Jump to content

Tet methylcytosine dioxygenase 1: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
m Fixed citation error
consistent citation formatting
 
(45 intermediate revisions by 27 users not shown)
Line 1: Line 1:
{{Short description|Mammalian protein found in Homo sapiens}}
{{PBB|geneid=80312}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
'''Ten-eleven translocation methylcytosine dioxygenase 1''' ('''TET1''') is a member of the TET family of [[enzyme]]s that in humans is encoded by the TET1 [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: Tet methylcytosine dioxygenase 1 | url = http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=80312 | accessdate = 2012-07-26 <!-- T20:28:02.557056-08:00 --> }}</ref><ref name = "Coulter_2013">{{cite journal | vauthors = Coulter JB, O'Driscoll CM, Bressler JP | title = Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase | journal = The Journal of Biological Chemistry | volume = 288 | issue = 40 | pages = 28792–800 | date = October 2013 | pmid = 23940045 | pmc = 3789975 | doi = 10.1074/jbc.M113.491365 }}</ref> It was first discovered in a 61 year old patient with a rare variation of t(10;11)(q22;q23) [[acute myeloid leukemia]]<nowiki/>a(AML)s a [[Zinc finger|zinc-finger]] binding protein (specifically on the CXXC domain) that fuses to the gene [[KMT2A|MLL.]]<ref>{{Cite journal|last=Ono|first=Ryoichi|last2=Taki|first2=Tomohiko|last3=Taketani|first3=Takeshi|last4=Taniwaki|first4=Masafumi|last5=Kobayashi|first5=Hajime|last6=Hayashi|first6=Yasuhide|date=2002-07-15|title=LCX, Leukemia-associated Protein with a CXXC Domain, Is Fused to MLL in Acute Myeloid Leukemia with Trilineage Dysplasia Having t(10;11)(q22;q23)|url=http://cancerres.aacrjournals.org/content/62/14/4075|journal=Cancer Research|language=en|volume=62|issue=14|pages=4075–4080|issn=0008-5472|pmid=12124344}}</ref> Another study confirmed that this protein was a [[Chromosomal translocation|translocation]] partner of MLL in an 8 year old patient with t(10;11)(q22;q23) AML and named the protein Ten-Eleven Translocation 1.<ref>{{Cite journal|last=Lorsbach|first=R. B.|last2=Moore|first2=J.|last3=Mathew|first3=S.|last4=Raimondi|first4=S. C.|last5=Mukatira|first5=S. T.|last6=Downing|first6=J. R.|date=2003-03-06|title=TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)|url=http://www.nature.com/leu/journal/v17/n3/full/2402834a.html|journal=Leukemia|language=en|volume=17|issue=3|pages=637–641|doi=10.1038/sj.leu.2402834|issn=0887-6924}}</ref>
{{Infobox_gene}}
'''Ten-eleven translocation methylcytosine dioxygenase 1''' ('''TET1''') is a member of the [[TET enzymes|TET family of enzymes]], in humans it is encoded by the TET1 gene. Its function, regulation, and utilizable pathways remain a matter of current research while it seems to be involved in [[DNA demethylation]] and therefore [[Regulation of gene expression|gene regulation,]]<ref name="entrez">{{cite web | title = Entrez Gene: Tet methylcytosine dioxygenase 1 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=80312 | access-date = 2012-07-26 <!-- T20:28:02.557056-08:00 --> }}</ref><ref name = "Coulter_2013">{{cite journal | vauthors = Coulter JB, O'Driscoll CM, Bressler JP | title = Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase | journal = The Journal of Biological Chemistry | volume = 288 | issue = 40 | pages = 28792–28800 | date = October 2013 | pmid = 23940045 | pmc = 3789975 | doi = 10.1074/jbc.M113.491365 | doi-access = free }}</ref> but is expressed as different isoforms which may have distinct functions.<ref name=":0">{{cite journal | vauthors = Yosefzon Y, David C, Tsukerman A, Pnueli L, Qiao S, Boehm U, Melamed P | title = An epigenetic switch repressing <i>Tet1</i> in gonadotropes activates the reproductive axis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 38 | pages = 10131–10136 | date = September 2017 | pmid = 28855337 | pmc = 5617270 | doi = 10.1073/pnas.1704393114 }}</ref><ref>{{cite journal | vauthors = Good CR, Madzo J, Patel B, Maegawa S, Engel N, Jelinek J, Issa JJ | title = A novel isoform of TET1 that lacks a CXXC domain is overexpressed in cancer | journal = Nucleic Acids Research | volume = 45 | issue = 14 | pages = 8269–8281 | date = August 2017 | pmid = 28531272 | pmc = 5737541 | doi = 10.1093/nar/gkx435 }}</ref>


== Discovery ==
⚫
TET1 [[catalysis|catalyzes]] the conversion of the modified [[DNA]] base [[5-methylcytosine]] (5-mC) to [[5-hydroxymethylcytosine]] (5-hmC).<ref name="Tahiliani_2009">{{cite journal | vauthors = Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A | title = Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 | journal = Science | volume = 324 | issue = 5929 | pages = 930–5 | date = May 2009 | pmid = 19372391 | pmc = 2715015 | doi = 10.1126/science.1170116 }}</ref> TET1 produces 5-hmC by [[oxidation]] of 5-mC in an [[iron]] and [[alpha-ketoglutarate]] dependent manner.<ref name="Ito_2010">{{cite journal | vauthors = Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y | title = Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine | journal = Science | volume = 333 | issue = 6047 | pages = 1300–3 | date = September 2011 | pmid = 21778364 | pmc = 3495246 | doi = 10.1126/science.1210597 }}</ref> The conversion of 5-mC to 5-hmC has been proposed as the initial step of active [[DNA demethylation]] in mammals.<ref name="Ito_2010"/> Additionally, downgrading TET1 has decreased levels of 5-formylcytosine (5-fC)  and 5-carboxylcytosine (5-caC) in both cell cultures and mice.<ref>{{cite journal | vauthors = Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y | title = Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine | journal = Science | volume = 333 | issue = 6047 | pages = 1300–3 | date = September 2011 | pmid = 21778364 | pmc = 3495246 | doi = 10.1126/science.1210597 }}</ref>


TET1 was first discovered in a 61-year-old patient with a rare variation of t(10;11)(q22;q23) [[acute myeloid leukemia|acute myeloid leukemia (AML)]] as a [[Zinc finger|zinc-finger]] binding protein (specifically on the CXXC domain) that fuses to the gene [[KMT2A|MLL.]]<ref>{{cite journal | vauthors = Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y | title = LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23) | journal = Cancer Research | volume = 62 | issue = 14 | pages = 4075–4080 | date = July 2002 | pmid = 12124344 }}</ref> Another study confirmed that this protein was a [[Chromosomal translocation|translocation]] partner of MLL in an 8-year-old patient with t(10;11)(q22;q23) AML and named the protein Ten-Eleven Translocation 1.<ref>{{cite journal | vauthors = Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR | title = TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23) | journal = Leukemia | volume = 17 | issue = 3 | pages = 637–641 | date = March 2003 | pmid = 12646957 | doi = 10.1038/sj.leu.2402834 | s2cid = 1202064 | doi-access = }}</ref>
⚫
TET1 appears to facilitate nuclear [[reprogramming]] of somatic cells to [[iPS cells]].<ref>{{cite journal | vauthors = Pera MF | title = Epigenetics, vitamin supplements and cellular reprogramming | journal = Nature Genetics | volume = 45 | issue = 12 | pages = 1412–3 | date = December 2013 | pmid = 24270443 | doi = 10.1038/ng.2834 | url = http://www.nature.com/ng/journal/v45/n12/full/ng.2834.html }}</ref>
⚫
<ref>{{cite journal | vauthors = Chen J, Gao Y, Huang H, Xu K, Chen X, Jiang Y, Li H, Gao S, Tao Y, Wang H, Zhang Y, Wang H, Cai T, Gao S | title = The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells | journal = Stem Cells | volume = 33 | issue = 3 | pages = 686–98 | date = March 2015 | pmid = 25331067 | doi = 10.1002/stem.1879 | url = http://onlinelibrary.wiley.com/doi/10.1002/stem.1879/abstract }}</ref> Patients with [[schizophrenia]] or [[bipolar disorder]] have shown increased levels of TET1 [[Messenger RNA|mRNA]] and protein expression in the [[inferior parietal lobule]], indicating these diseases may be caused by mistakes in gene expression regulation.<ref>{{cite journal | vauthors = Dong E, Gavin DP, Chen Y, Davis J | title = Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients | journal = Translational Psychiatry | volume = 2 | issue = 9 | pages = e159 | date = 2012-09-01 | pmid = 22948384 | pmc = 3565208 | doi = 10.1038/tp.2012.86 }}</ref>


== Function ==
⚫
Colon, breast, prostate and liver tumors have significantly reduced levels of TET1 compared to the healthy colon cells and normal epithelial colon cells with downgraded TET1 levels have greater levels of proliferation.<ref>{{cite journal | vauthors = Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, Guan KL, Xiong Y | title = Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation | journal = Oncogene | volume = 32 | issue = 5 | pages = 663–9 | date = January 2013 | pmid = 22391558 | pmc = 3897214 | doi = 10.1038/onc.2012.67 }}</ref><ref name="Neri_2015">{{cite journal | vauthors = Neri F, Dettori D, Incarnato D, Krepelova A, Rapelli S, Maldotti M, Parlato C, Paliogiannis P, Oliviero S | title = TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway | language = en | journal = Oncogene | volume = 34 | issue = 32 | pages = 4168–76 | date = August 2015 | pmid = 25362856 | doi = 10.1038/onc.2014.356 }}</ref><ref>{{Cite journal|last=Liu|first=Chungang|last2=Liu|first2=Limei|last3=Chen|first3=Xuejiao|last4=Shen|first4=Junjie|last5=Shan|first5=Juanjuan|last6=Xu|first6=Yanmin|last7=Yang|first7=Zhi|last8=Wu|first8=Lin|last9=Xia|first9=Feng|date=2013-05-09|title=Decrease of 5-Hydroxymethylcytosine Is Associated with Progression of Hepatocellular Carcinoma through Downregulation of TET1|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650038/|journal=PLoS ONE|volume=8|issue=5|doi=10.1371/journal.pone.0062828|issn=1932-6203|pmc=3650038|pmid=23671639}}</ref><ref name=":1">{{Cite journal|last=Hsu|first=Chih-Hung|last2=Peng|first2=Kai-Lin|last3=Kang|first3=Ming-Lun|last4=Chen|first4=Yi-Ren|last5=Yang|first5=Yu-Chih|last6=Tsai|first6=Chin-Hsien|last7=Chu|first7=Chi-Shuen|last8=Jeng|first8=Yung-Ming|last9=Chen|first9=Yen-Ting|date=2012-09-27|title=TET1 Suppresses Cancer Invasion by Activating the Tissue Inhibitors of Metalloproteinases|url=http://www.cell.com/article/S2211124712002707/abstract|journal=Cell Reports|language=English|volume=2|issue=3|pages=568–579|doi=10.1016/j.celrep.2012.08.030|issn=2211-1247|pmid=22999938}}</ref> Additionally, increasing TET1 expression levels in colon [[cancer]] cells decreased cell proliferation in both cell cultures and mice through [[demethylation]] of promoters of the [[Wnt signaling pathway|WNT signaling pathway]].<ref name="Neri_2015"/>.


TET1 [[catalysis|catalyzes]] the conversion of the modified [[DNA]] base [[5-methylcytosine]] (5-mC) to [[5-hydroxymethylcytosine]] (5-hmC).<ref name="Tahiliani_2009">{{cite journal | vauthors = Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A | title = Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 | journal = Science | volume = 324 | issue = 5929 | pages = 930–935 | date = May 2009 | pmid = 19372391 | pmc = 2715015 | doi = 10.1126/science.1170116 | bibcode = 2009Sci...324..930T }}</ref>
⚫
Breast cancer cell lines with silenced TET1 expression have increased rates of invasion and breast cancers that spread to the lymph nodes are characterized by lower TET1 levels.<ref name=":0">{{Cite journal|last=Sang|first=Yi|last2=Cheng|first2=Chun|last3=Tang|first3=Xiao-Feng|last4=Zhang|first4=Mei-Fang|last5=Lv|first5=Xiao-Bin|date=2015-01-01|title=Hypermethylation of TET1 promoter is a new diagnosic marker for breast cancer metastasis|url=http://www.ncbi.nlm.nih.gov/pubmed/25735355|journal=Asian Pacific journal of cancer prevention: APJCP|volume=16|issue=3|pages=1197–1200|issn=1513-7368|pmid=25735355}}</ref> TET1 levels could be used to detect breast cancer metastasis.<ref name=":0" /> A [[histone deacetylase inhibitor]] Trichostatin A increased levels of TET1 in breast cancer tissues but was a less effective tumor suppressor in patients with low TET1 expression.<ref>{{Cite web|url=http://www.spandidos-publications.com/mmr/10/5/2595#f1-mmr-10-05-2595|title=TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion|website=www.spandidos-publications.com|access-date=2016-04-07}}</ref> Breast cancer patients with high TET1 levels had significantly higher survival probabilities than patients with low TET1 levels.<ref name=":1" />


:[[File:Reaction catalyzed by Tet methylcytosine dioxygenase 1 - en.svg|thumb|left|300px]]{{clear-left}}
⚫
Degradation of TET1 in hypoxnia-induced [[Epithelial–mesenchymal transition|EMT]] lung cancer cells led to reduced metastasis rates and cells.<ref>{{Cite journal|last=Tsai|first=Ya-Ping|last2=Chen|first2=Hsiao-Fan|last3=Chen|first3=Sung-Yuan|last4=Cheng|first4=Wei-Chung|last5=Wang|first5=Hsei-Wei|last6=Shen|first6=Zih-Jie|last7=Song|first7=Chunxiao|last8=Teng|first8=Shu-Chun|last9=He|first9=Chuan|date=2014-01-01|title=TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253621/|journal=Genome Biology|volume=15|issue=12|doi=10.1186/s13059-014-0513-0|issn=1465-6906|pmc=4253621|pmid=25517638}}</ref> Healthy cells transitioning to cancer cells have decreased levels of TET1 but decreasing TET1 expression does not lead to [[Malignacy|malignancy]].<ref>{{Cite journal|last=Kudo|first=Yotaro|last2=Tateishi|first2=Keisuke|last3=Yamamoto|first3=Keisuke|last4=Yamamoto|first4=Shinzo|last5=Asaoka|first5=Yoshinari|last6=Ijichi|first6=Hideaki|last7=Nagae|first7=Genta|last8=Yoshida|first8=Haruhiko|last9=Aburatani|first9=Hiroyuki|date=2012-04-01|title=Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation|url=http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2012.02213.x/abstract|journal=Cancer Science|language=en|volume=103|issue=4|pages=670–676|doi=10.1111/j.1349-7006.2012.02213.x|issn=1349-7006}}</ref> Cancer cells using the [[KRAS]] pathway had decreased invasive potential after reintroducing TET1, likewise downgrading KRAS increased TET1 levels.<ref>{{Cite journal|last=Wu|first=Bo-Kuan|last2=Brenner|first2=Charles|date=2014-12-11|title=Suppression of TET1-Dependent DNA Demethylation is Essential for KRAS-Mediated Transformation|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4268240/|journal=Cell reports|volume=9|issue=5|pages=1827–1840|doi=10.1016/j.celrep.2014.10.063|issn=2211-1247|pmc=4268240|pmid=25466250}}</ref>

⚫
TET1 produces 5-hmC by [[oxidation]] of 5-mC in an [[iron]] and [[alpha-ketoglutarate]] dependent manner.<ref name="Ito_2010">{{cite journal | vauthors = Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, He C, Zhang Y | title = Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine | journal = Science | volume = 333 | issue = 6047 | pages = 1300–1303 | date = September 2011 | pmid = 21778364 | pmc = 3495246 | doi = 10.1126/science.1210597 | bibcode = 2011Sci...333.1300I }}</ref> The conversion of 5-mC to 5-hmC has been proposed as the initial step of active [[DNA demethylation]] in mammals.<ref name="Ito_2010"/> Additionally, downgrading TET1 has decreased levels of 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC) in both cell cultures and mice.<ref name="Ito_2010"/>

A site with a 5-hmC base already has increased transcriptional activity, a state termed "functional demethylation". This state is common in post-mitotic [[neuron]]s.<ref>{{cite journal | vauthors = Mellén M, Ayata P, Heintz N | title = 5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 37 | pages = E7812-E7821 | date = September 2017 | pmid = 28847947 | pmc = 5604027 | doi = 10.1073/pnas.1708044114 | doi-access = free | bibcode = 2017PNAS..114E7812M }}</ref> However it has also been found to inhibit transcription of some genes, and is associated with various transcriptional repressors, especially PRC2 complex, suggesting diverse modes of action.<ref>{{cite journal | vauthors = Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, Helin K | title = TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity | journal = Nature | volume = 473 | issue = 7347 | pages = 343–348 | date = May 2011 | pmid = 21490601 | pmc = 3408592 | doi = 10.1038/nature10066 }}</ref><ref>{{cite journal | vauthors = Wu H, D'Alessio AC, Ito S, Xia K, Wang Z, Cui K, Zhao K, Sun YE, Zhang Y | title = Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells | journal = Nature | volume = 473 | issue = 7347 | pages = 389–393 | date = May 2011 | pmid = 21451524 | pmc = 3539771 | doi = 10.1038/nature09934 }}</ref><ref name=":0" />

TET1 may play a role in [[memory extinction]]. TET1-[[Knockout mouse|knockout mice]] show markedly impaired memory extinction, despite maintaining normal memory acquisition.<ref>{{cite journal | vauthors = Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J, Le T, Faull KF, Jaenisch R, Tsai LH | title = Tet1 is critical for neuronal activity-regulated gene expression and memory extinction | journal = Neuron | volume = 79 | issue = 6 | pages = 1109–1122 | date = September 2013 | pmid = 24050401 | pmc = 4543319 | doi = 10.1016/j.neuron.2013.08.003 }}</ref>

== Applications ==

⚫
TET1 appears to facilitate nuclear [[reprogramming]] of somatic cells to [[iPS cells]].<ref>{{cite journal | vauthors = Pera MF | title = Epigenetics, vitamin supplements and cellular reprogramming | journal = Nature Genetics | volume = 45 | issue = 12 | pages = 1412–1413 | date = December 2013 | pmid = 24270443 | doi = 10.1038/ng.2834 | s2cid = 11597504 }}</ref><ref>{{cite journal | vauthors = Chen J, Gao Y, Huang H, Xu K, Chen X, Jiang Y, Li H, Gao S, Tao Y, Wang H, Zhang Y, Wang H, Cai T, Gao S | title = The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells | journal = Stem Cells | volume = 33 | issue = 3 | pages = 686–698 | date = March 2015 | pmid = 25331067 | doi = 10.1002/stem.1879 | s2cid = 42714024 | doi-access = free }}</ref>

The enzyme is also utilized as part of TET-Assisted Bisulfite Sequencing (TAB-seq) to quantify levels of hydroxymethylation in the genome and to distinguish 5-hydroxymethylcytosine (5hmc) from 5-methylcytosine (5mc) at single base resolution. The technique was developed by Chuan He and rectifies the inability of traditional bisulfite sequencing to decipher between the two modified bases. In this technique, TET1 is responsible for the oxidation of 5mc allowing it to be read as thymine following treatment with bisulfite. This is not the case for 5hmc as it is glucosylated in the initial step inhibiting its oxidation by TET1.

== Clinical significance ==

⚫
Patients with [[schizophrenia]] or [[bipolar disorder]] have shown increased levels of TET1 [[Messenger RNA|mRNA]] and protein expression in the [[inferior parietal lobule]], indicating these diseases may be caused by mistakes in gene expression regulation.<ref>{{cite journal | vauthors = Dong E, Gavin DP, Chen Y, Davis J | title = Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients | journal = Translational Psychiatry | volume = 2 | issue = 9 | pages = e159 | date = September 2012 | pmid = 22948384 | pmc = 3565208 | doi = 10.1038/tp.2012.86 }}</ref>

⚫
Colon, breast, prostate and liver tumors have significantly reduced levels of TET1 compared to the healthy colon cells and normal epithelial colon cells with downgraded TET1 levels have greater levels of proliferation.<ref>{{cite journal | vauthors = Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, Xu ZD, Zhu HG, Ling ZQ, Ye D, Guan KL, Xiong Y | title = Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation | journal = Oncogene | volume = 32 | issue = 5 | pages = 663–669 | date = January 2013 | pmid = 22391558 | pmc = 3897214 | doi = 10.1038/onc.2012.67 }}</ref><ref name="Neri_2015">{{cite journal | vauthors = Neri F, Dettori D, Incarnato D, Krepelova A, Rapelli S, Maldotti M, Parlato C, Paliogiannis P, Oliviero S | title = TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway | journal = Oncogene | volume = 34 | issue = 32 | pages = 4168–4176 | date = August 2015 | pmid = 25362856 | doi = 10.1038/onc.2014.356 | s2cid = 22017396 | doi-access = free | hdl = 2318/150019 | hdl-access = free }}</ref><ref>{{cite journal | vauthors = Liu C, Liu L, Chen X, Shen J, Shan J, Xu Y, Yang Z, Wu L, Xia F, Bie P, Cui Y, Bian XW, Qian C | title = Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1 | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e62828 | date = 2013-05-09 | pmid = 23671639 | pmc = 3650038 | doi = 10.1371/journal.pone.0062828 | doi-access = free | bibcode = 2013PLoSO...862828L }}</ref><ref name="Hsu_2012">{{cite journal | vauthors = Hsu CH, Peng KL, Kang ML, Chen YR, Yang YC, Tsai CH, Chu CS, Jeng YM, Chen YT, Lin FM, Huang HD, Lu YY, Teng YC, Lin ST, Lin RK, Tang FM, Lee SB, Hsu HM, Yu JC, Hsiao PW, Juan LJ | title = TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases | journal = Cell Reports | volume = 2 | issue = 3 | pages = 568–579 | date = September 2012 | pmid = 22999938 | doi = 10.1016/j.celrep.2012.08.030 | doi-access = free }}</ref> Additionally, increasing TET1 expression levels in colon [[cancer]] cells decreased cell proliferation in both cell cultures and mice through [[demethylation]] of promoters of the [[Wnt signaling pathway|WNT signaling pathway]].<ref name="Neri_2015"/>

⚫
Breast cancer cell lines with silenced TET1 expression have increased rates of invasion and breast cancers that spread to the lymph nodes are characterized by lower TET1 levels.<ref name="Sang_2015">{{cite journal | vauthors = Sang Y, Cheng C, Tang XF, Zhang MF, Lv XB | title = Hypermethylation of TET1 promoter is a new diagnosic marker for breast cancer metastasis | journal = Asian Pacific Journal of Cancer Prevention | volume = 16 | issue = 3 | pages = 1197–1200 | date = 2015-01-01 | pmid = 25735355 | doi = 10.7314/apjcp.2015.16.3.1197 | doi-access = free }}</ref> TET1 levels could be used to detect breast cancer metastasis.<ref name="Sang_2015" /> A [[histone deacetylase inhibitor]] Trichostatin A increased levels of TET1 in breast cancer tissues but was a less effective tumor suppressor in patients with low TET1 expression.<ref>{{cite journal | vauthors = Lu HG, Zhan W, Yan L, Qin RY, Yan YP, Yang ZJ, Liu GC, Li GQ, Wang HF, Li XL, Li Z, Gao L, Chen GQ | title = TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion | journal = Molecular Medicine Reports | volume = 10 | issue = 5 | pages = 2595–2600 | date = November 2014 | pmid = 25175940 | doi = 10.3892/mmr.2014.2517 | doi-access = free }}</ref> Breast cancer patients with high TET1 levels had significantly higher survival probabilities than patients with low TET1 levels.<ref name="Hsu_2012"/>

⚫
Degradation of TET1 in hypoxia-induced [[Epithelial–mesenchymal transition|EMT]] lung cancer cells led to reduced metastasis rates and cells.<ref>{{cite journal | vauthors = Tsai YP, Chen HF, Chen SY, Cheng WC, Wang HW, Shen ZJ, Song C, Teng SC, He C, Wu KJ | title = TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator | journal = Genome Biology | volume = 15 | issue = 12 | pages = 513 | date = December 2014 | pmid = 25517638 | pmc = 4253621 | doi = 10.1186/s13059-014-0513-0 | doi-access = free }}</ref> Healthy cells transitioning to cancer cells have decreased levels of TET1 but decreasing TET1 expression does not lead to [[malignancy]].<ref>{{cite journal | vauthors = Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, Nagae G, Yoshida H, Aburatani H, Koike K | title = Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation | journal = Cancer Science | volume = 103 | issue = 4 | pages = 670–676 | date = April 2012 | pmid = 22320381 | pmc = 7659252 | doi = 10.1111/j.1349-7006.2012.02213.x | s2cid = 5823834 | doi-access = free }}</ref> Cancer cells using the [[KRAS]] pathway had decreased invasive potential after reintroducing TET1, likewise downgrading KRAS increased TET1 levels.<ref>{{cite journal | vauthors = Wu BK, Brenner C | title = Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation | journal = Cell Reports | volume = 9 | issue = 5 | pages = 1827–1840 | date = December 2014 | pmid = 25466250 | pmc = 4268240 | doi = 10.1016/j.celrep.2014.10.063 }}</ref>


== References ==
== References ==
{{reflist}}
{{reflist|33em}}

{{-}}
== Further reading ==
== Further reading ==
{{refbegin|33em}}
{{refbegin|33em}}
* {{cite journal | vauthors = Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, Huberman K, Thomas S, Dolgalev I, Heguy A, Paietta E, Le Beau MM, Beran M, Tallman MS, Ebert BL, Kantarjian HM, Stone RM, Gilliland DG, Crispino JD, Levine RL | title = Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies | journal = Blood | volume = 114 | issue = 1 | pages = 144–7 | date = July 2009 | pmid = 19420352 | pmc = 2710942 | doi = 10.1182/blood-2009-03-210039 }}
* {{cite journal | vauthors = Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M, Malinge S, Yao J, Kilpivaara O, Bhat R, Huberman K, Thomas S, Dolgalev I, Heguy A, Paietta E, Le Beau MM, Beran M, Tallman MS, Ebert BL, Kantarjian HM, Stone RM, Gilliland DG, Crispino JD, Levine RL | title = Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies | journal = Blood | volume = 114 | issue = 1 | pages = 144–147 | date = July 2009 | pmid = 19420352 | pmc = 2710942 | doi = 10.1182/blood-2009-03-210039 }}
* {{cite journal | vauthors = Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR | title = TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23) | journal = Leukemia | volume = 17 | issue = 3 | pages = 637–41 | date = March 2003 | pmid = 12646957 | pmc = | doi = 10.1038/sj.leu.2402834 }}
* {{cite journal | vauthors = Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR | title = TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23) | journal = Leukemia | volume = 17 | issue = 3 | pages = 637–641 | date = March 2003 | pmid = 12646957 | doi = 10.1038/sj.leu.2402834 | s2cid = 1202064 | doi-access = }}
* {{cite journal | vauthors = Morgan AR, Hamilton G, Turic D, Jehu L, Harold D, Abraham R, Hollingworth P, Moskvina V, Brayne C, Rubinsztein DC, Lynch A, Lawlor B, Gill M, O'Donovan M, Powell J, Lovestone S, Williams J, Owen MJ | title = Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 147B | issue = 6 | pages = 727–31 | date = September 2008 | pmid = 18163421 | pmc = | doi = 10.1002/ajmg.b.30670 }}
* {{cite journal | vauthors = Morgan AR, Hamilton G, Turic D, Jehu L, Harold D, Abraham R, Hollingworth P, Moskvina V, Brayne C, Rubinsztein DC, Lynch A, Lawlor B, Gill M, O'Donovan M, Powell J, Lovestone S, Williams J, Owen MJ | title = Association analysis of 528 intra-genic SNPs in a region of chromosome 10 linked to late onset Alzheimer's disease | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 147B | issue = 6 | pages = 727–731 | date = September 2008 | pmid = 18163421 | doi = 10.1002/ajmg.b.30670 | s2cid = 13916214 }}
* {{cite journal | vauthors = Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y | title = LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23) | journal = Cancer Research | volume = 62 | issue = 14 | pages = 4075–80 | date = July 2002 | pmid = 12124344 }}
* {{cite journal | vauthors = Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y | title = LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23) | journal = Cancer Research | volume = 62 | issue = 14 | pages = 4075–4080 | date = July 2002 | pmid = 12124344 }}
* {{cite journal | vauthors = Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y | title = Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases | journal = Cancer Cell | volume = 19 | issue = 1 | pages = 17–30 | date = January 2011 | pmid = 21251613 | pmc = 3229304 | doi = 10.1016/j.ccr.2010.12.014 }}
* {{cite journal | vauthors = Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y | title = Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases | journal = Cancer Cell | volume = 19 | issue = 1 | pages = 17–30 | date = January 2011 | pmid = 21251613 | pmc = 3229304 | doi = 10.1016/j.ccr.2010.12.014 }}
* {{cite journal | vauthors = Guo JU, Su Y, Zhong C, Ming GL, Song H | title = Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain | journal = Cell | volume = 145 | issue = 3 | pages = 423–34 | date = April 2011 | pmid = 21496894 | pmc = 3088758 | doi = 10.1016/j.cell.2011.03.022 }}
* {{cite journal | vauthors = Guo JU, Su Y, Zhong C, Ming GL, Song H | title = Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain | journal = Cell | volume = 145 | issue = 3 | pages = 423–434 | date = April 2011 | pmid = 21496894 | pmc = 3088758 | doi = 10.1016/j.cell.2011.03.022 }}
* {{cite journal | vauthors = Frauer C, Rottach A, Meilinger D, Bultmann S, Fellinger K, Hasenöder S, Wang M, Qin W, Söding J, Spada F, Leonhardt H | title = Different binding properties and function of CXXC zinc finger domains in Dnmt1 and Tet1 | journal = PloS One | volume = 6 | issue = 2 | pages = e16627 | year = 2011 | pmid = 21311766 | pmc = 3032784 | doi = 10.1371/journal.pone.0016627 }}
* {{cite journal | vauthors = Frauer C, Rottach A, Meilinger D, Bultmann S, Fellinger K, Hasenöder S, Wang M, Qin W, Söding J, Spada F, Leonhardt H | title = Different binding properties and function of CXXC zinc finger domains in Dnmt1 and Tet1 | journal = PLOS ONE | volume = 6 | issue = 2 | pages = e16627 | date = February 2011 | pmid = 21311766 | pmc = 3032784 | doi = 10.1371/journal.pone.0016627 | doi-access = free | bibcode = 2011PLoSO...616627F }}
* {{cite journal | vauthors = Langemeijer SM, Aslanyan MG, Jansen JH | title = TET proteins in malignant hematopoiesis | journal = Cell Cycle | volume = 8 | issue = 24 | pages = 4044–8 | date = December 2009 | pmid = 19923888 | doi = 10.4161/cc.8.24.10239 }}
* {{cite journal | vauthors = Langemeijer SM, Aslanyan MG, Jansen JH | title = TET proteins in malignant hematopoiesis | journal = Cell Cycle | volume = 8 | issue = 24 | pages = 4044–4048 | date = December 2009 | pmid = 19923888 | doi = 10.4161/cc.8.24.10239 | s2cid = 27430810 | doi-access = }}
* {{cite journal | vauthors = Mohr F, Döhner K, Buske C, Rawat VP | title = TET genes: new players in DNA demethylation and important determinants for stemness | journal = Experimental Hematology | volume = 39 | issue = 3 | pages = 272–81 | date = March 2011 | pmid = 21168469 | doi = 10.1016/j.exphem.2010.12.004 }}
* {{cite journal | vauthors = Mohr F, Döhner K, Buske C, Rawat VP | title = TET genes: new players in DNA demethylation and important determinants for stemness | journal = Experimental Hematology | volume = 39 | issue = 3 | pages = 272–281 | date = March 2011 | pmid = 21168469 | doi = 10.1016/j.exphem.2010.12.004 | doi-access = free }}
{{refend}}
{{refend}}


{{Dioxygenases}}
{{Dioxygenases}}
{{Enzymes}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}
{{Portal bar|Biology|border=no}}

{{gene-10-stub}}


[[Category:EC 1.14.11]]
[[Category:EC 1.14.11]]

Latest revision as of 21:28, 14 December 2024

TET1
Identifiers
AliasesTET1, CXXC6, LCX, bA119F7.1, MLL-TET1-MLL, Tet methylcytosine dioxygenase 1
External IDsOMIM: 607790; MGI: 1098693; HomoloGene: 12735; GeneCards: TET1; OMA:TET1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

80312

52463

Ensembl

ENSG00000138336

ENSMUSG00000047146

UniProt

Q8NFU7

Q3URK3

RefSeq (mRNA)

NM_030625

NM_001253857
NM_027384

RefSeq (protein)

NP_085128

NP_001240786
NP_001393310
NP_001393311
NP_001393312

Location (UCSC)Chr 10: 68.56 – 68.69 MbChr 10: 62.64 – 62.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, in humans it is encoded by the TET1 gene. Its function, regulation, and utilizable pathways remain a matter of current research while it seems to be involved in DNA demethylation and therefore gene regulation,[5][6] but is expressed as different isoforms which may have distinct functions.[7][8]

Discovery

[edit]

TET1 was first discovered in a 61-year-old patient with a rare variation of t(10;11)(q22;q23) acute myeloid leukemia (AML) as a zinc-finger binding protein (specifically on the CXXC domain) that fuses to the gene MLL.[9] Another study confirmed that this protein was a translocation partner of MLL in an 8-year-old patient with t(10;11)(q22;q23) AML and named the protein Ten-Eleven Translocation 1.[10]

Function

[edit]

TET1 catalyzes the conversion of the modified DNA base 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC).[11]

TET1 produces 5-hmC by oxidation of 5-mC in an iron and alpha-ketoglutarate dependent manner.[12] The conversion of 5-mC to 5-hmC has been proposed as the initial step of active DNA demethylation in mammals.[12] Additionally, downgrading TET1 has decreased levels of 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC) in both cell cultures and mice.[12]

A site with a 5-hmC base already has increased transcriptional activity, a state termed "functional demethylation". This state is common in post-mitotic neurons.[13] However it has also been found to inhibit transcription of some genes, and is associated with various transcriptional repressors, especially PRC2 complex, suggesting diverse modes of action.[14][15][7]

TET1 may play a role in memory extinction. TET1-knockout mice show markedly impaired memory extinction, despite maintaining normal memory acquisition.[16]

Applications

[edit]

TET1 appears to facilitate nuclear reprogramming of somatic cells to iPS cells.[17][18]

The enzyme is also utilized as part of TET-Assisted Bisulfite Sequencing (TAB-seq) to quantify levels of hydroxymethylation in the genome and to distinguish 5-hydroxymethylcytosine (5hmc) from 5-methylcytosine (5mc) at single base resolution. The technique was developed by Chuan He and rectifies the inability of traditional bisulfite sequencing to decipher between the two modified bases. In this technique, TET1 is responsible for the oxidation of 5mc allowing it to be read as thymine following treatment with bisulfite. This is not the case for 5hmc as it is glucosylated in the initial step inhibiting its oxidation by TET1.

Clinical significance

[edit]

Patients with schizophrenia or bipolar disorder have shown increased levels of TET1 mRNA and protein expression in the inferior parietal lobule, indicating these diseases may be caused by mistakes in gene expression regulation.[19]

Colon, breast, prostate and liver tumors have significantly reduced levels of TET1 compared to the healthy colon cells and normal epithelial colon cells with downgraded TET1 levels have greater levels of proliferation.[20][21][22][23] Additionally, increasing TET1 expression levels in colon cancer cells decreased cell proliferation in both cell cultures and mice through demethylation of promoters of the WNT signaling pathway.[21]

Breast cancer cell lines with silenced TET1 expression have increased rates of invasion and breast cancers that spread to the lymph nodes are characterized by lower TET1 levels.[24] TET1 levels could be used to detect breast cancer metastasis.[24] A histone deacetylase inhibitor Trichostatin A increased levels of TET1 in breast cancer tissues but was a less effective tumor suppressor in patients with low TET1 expression.[25] Breast cancer patients with high TET1 levels had significantly higher survival probabilities than patients with low TET1 levels.[23]

Degradation of TET1 in hypoxia-induced EMT lung cancer cells led to reduced metastasis rates and cells.[26] Healthy cells transitioning to cancer cells have decreased levels of TET1 but decreasing TET1 expression does not lead to malignancy.[27] Cancer cells using the KRAS pathway had decreased invasive potential after reintroducing TET1, likewise downgrading KRAS increased TET1 levels.[28]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138336 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000047146 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Tet methylcytosine dioxygenase 1". Retrieved 2012-07-26.
  6. ^ Coulter JB, O'Driscoll CM, Bressler JP (October 2013). "Hydroquinone increases 5-hydroxymethylcytosine formation through ten eleven translocation 1 (TET1) 5-methylcytosine dioxygenase". The Journal of Biological Chemistry. 288 (40): 28792–28800. doi:10.1074/jbc.M113.491365. PMC 3789975. PMID 23940045.
  7. ^ a b Yosefzon Y, David C, Tsukerman A, Pnueli L, Qiao S, Boehm U, et al. (September 2017). "An epigenetic switch repressing Tet1 in gonadotropes activates the reproductive axis". Proceedings of the National Academy of Sciences of the United States of America. 114 (38): 10131–10136. doi:10.1073/pnas.1704393114. PMC 5617270. PMID 28855337.
  8. ^ Good CR, Madzo J, Patel B, Maegawa S, Engel N, Jelinek J, et al. (August 2017). "A novel isoform of TET1 that lacks a CXXC domain is overexpressed in cancer". Nucleic Acids Research. 45 (14): 8269–8281. doi:10.1093/nar/gkx435. PMC 5737541. PMID 28531272.
  9. ^ Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y (July 2002). "LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23)". Cancer Research. 62 (14): 4075–4080. PMID 12124344.
  10. ^ Lorsbach RB, Moore J, Mathew S, Raimondi SC, Mukatira ST, Downing JR (March 2003). "TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)". Leukemia. 17 (3): 637–641. doi:10.1038/sj.leu.2402834. PMID 12646957. S2CID 1202064.
  11. ^ Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, et al. (May 2009). "Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1". Science. 324 (5929): 930–935. Bibcode:2009Sci...324..930T. doi:10.1126/science.1170116. PMC 2715015. PMID 19372391.
  12. ^ a b c Ito S, Shen L, Dai Q, Wu SC, Collins LB, Swenberg JA, et al. (September 2011). "Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine". Science. 333 (6047): 1300–1303. Bibcode:2011Sci...333.1300I. doi:10.1126/science.1210597. PMC 3495246. PMID 21778364.
  13. ^ Mellén M, Ayata P, Heintz N (September 2017). "5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes". Proceedings of the National Academy of Sciences of the United States of America. 114 (37): E7812–E7821. Bibcode:2017PNAS..114E7812M. doi:10.1073/pnas.1708044114. PMC 5604027. PMID 28847947.
  14. ^ Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, et al. (May 2011). "TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity". Nature. 473 (7347): 343–348. doi:10.1038/nature10066. PMC 3408592. PMID 21490601.
  15. ^ Wu H, D'Alessio AC, Ito S, Xia K, Wang Z, Cui K, et al. (May 2011). "Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells". Nature. 473 (7347): 389–393. doi:10.1038/nature09934. PMC 3539771. PMID 21451524.
  16. ^ Rudenko A, Dawlaty MM, Seo J, Cheng AW, Meng J, Le T, et al. (September 2013). "Tet1 is critical for neuronal activity-regulated gene expression and memory extinction". Neuron. 79 (6): 1109–1122. doi:10.1016/j.neuron.2013.08.003. PMC 4543319. PMID 24050401.
  17. ^ Pera MF (December 2013). "Epigenetics, vitamin supplements and cellular reprogramming". Nature Genetics. 45 (12): 1412–1413. doi:10.1038/ng.2834. PMID 24270443. S2CID 11597504.
  18. ^ Chen J, Gao Y, Huang H, Xu K, Chen X, Jiang Y, et al. (March 2015). "The combination of Tet1 with Oct4 generates high-quality mouse-induced pluripotent stem cells". Stem Cells. 33 (3): 686–698. doi:10.1002/stem.1879. PMID 25331067. S2CID 42714024.
  19. ^ Dong E, Gavin DP, Chen Y, Davis J (September 2012). "Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients". Translational Psychiatry. 2 (9): e159. doi:10.1038/tp.2012.86. PMC 3565208. PMID 22948384.
  20. ^ Yang H, Liu Y, Bai F, Zhang JY, Ma SH, Liu J, et al. (January 2013). "Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation". Oncogene. 32 (5): 663–669. doi:10.1038/onc.2012.67. PMC 3897214. PMID 22391558.
  21. ^ a b Neri F, Dettori D, Incarnato D, Krepelova A, Rapelli S, Maldotti M, et al. (August 2015). "TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway". Oncogene. 34 (32): 4168–4176. doi:10.1038/onc.2014.356. hdl:2318/150019. PMID 25362856. S2CID 22017396.
  22. ^ Liu C, Liu L, Chen X, Shen J, Shan J, Xu Y, et al. (2013-05-09). "Decrease of 5-hydroxymethylcytosine is associated with progression of hepatocellular carcinoma through downregulation of TET1". PLOS ONE. 8 (5): e62828. Bibcode:2013PLoSO...862828L. doi:10.1371/journal.pone.0062828. PMC 3650038. PMID 23671639.
  23. ^ a b Hsu CH, Peng KL, Kang ML, Chen YR, Yang YC, Tsai CH, et al. (September 2012). "TET1 suppresses cancer invasion by activating the tissue inhibitors of metalloproteinases". Cell Reports. 2 (3): 568–579. doi:10.1016/j.celrep.2012.08.030. PMID 22999938.
  24. ^ a b Sang Y, Cheng C, Tang XF, Zhang MF, Lv XB (2015-01-01). "Hypermethylation of TET1 promoter is a new diagnosic marker for breast cancer metastasis". Asian Pacific Journal of Cancer Prevention. 16 (3): 1197–1200. doi:10.7314/apjcp.2015.16.3.1197. PMID 25735355.
  25. ^ Lu HG, Zhan W, Yan L, Qin RY, Yan YP, Yang ZJ, et al. (November 2014). "TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion". Molecular Medicine Reports. 10 (5): 2595–2600. doi:10.3892/mmr.2014.2517. PMID 25175940.
  26. ^ Tsai YP, Chen HF, Chen SY, Cheng WC, Wang HW, Shen ZJ, et al. (December 2014). "TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator". Genome Biology. 15 (12): 513. doi:10.1186/s13059-014-0513-0. PMC 4253621. PMID 25517638.
  27. ^ Kudo Y, Tateishi K, Yamamoto K, Yamamoto S, Asaoka Y, Ijichi H, et al. (April 2012). "Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation". Cancer Science. 103 (4): 670–676. doi:10.1111/j.1349-7006.2012.02213.x. PMC 7659252. PMID 22320381. S2CID 5823834.
  28. ^ Wu BK, Brenner C (December 2014). "Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation". Cell Reports. 9 (5): 1827–1840. doi:10.1016/j.celrep.2014.10.063. PMC 4268240. PMID 25466250.

Further reading

[edit]
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Tet_methylcytosine_dioxygenase_1&oldid=1263128871"