Jump to content

User:AAR3643/Epigenetic regulation of neurogenesis

From Wikipedia, the free encyclopedia
< User:AAR3643

This is an old revision of this page, as edited by Theflyelectric (talk | contribs) at 20:59, 29 April 2022 (→Histone modifications (cleanup edit)). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Sandbox belonging to Andre Ribeiro, Amulya Cherian, and Andrew Spires.

Trevor's comments in magenta

Article Draft

Edit Outline Summary

We are proposing to make edits to the article Epigenetic regulation of neurogenesis. This article is rated as start-class on the article's talk page and as such there were various changes that we wished to make to improve the overall breadth of information covered by the article.  In particular, while there is relatively decent coverage of information within this article regarding epigenetic factors involved in embryonic neurogenesis, the information regarding adult neurogenesis is rather lacking in depth, and includes many topics that are essentially thrown in randomly without being discussed further or elaborated upon to paint a coherent picture.

Histone Modifications Edits: For example, one of the changes we proposed was adding an explanation of HDAC and HAT activity into the "histone modifications" subtopic within the overarching topic “Adult neurogenesis,” as well as expanding the subtopic to include more than simply the effects of histone deacetylation alone, as is present in the original article. This explanation for HDAC and HAT activity would include their overall functions of removing and adding acetyl groups to histone tails, respectively, as well as the use of HDAC inhibitors (HDACi’s) trichostatin A and valproic acid, which not only induce neuronal differentiation in embryos and lead to neurogenesis, but also inhibit the differentiation of glial cells in adult neural stem cells as well [1] Upon reading the review article, these histone modifications and their reversal by mechanisms such as HDACs and their respective inhibitors are vital in the regulation of adult neurogenesis, and as such, we believe their inclusion within this article would be essential in ameliorating a few of its shortcomings.

miRNAs: In addition, we would also like to expand the discussions on both the miRNA and methylation-specific effects on neurogenesis, as the article discusses them briefly using only one to two sources each to support their arguments. These miRNA effects are of particular interest, seeing as researchers have discovered that less than three percent of the entire human genome encodes proteins. [2] As a result, a great majority of the remaining genome is transcribed to a multitude of RNA’s, including miRNAs. While certain miRNAs are well-documented to play significant roles in neurogenesis and included within the current article, including both miR-9 and miR-124 which are particularly abundant in the human brain, other miRNAs including miR-137, miR-184 and miR-195 play vital functions in the proliferation of neurons in the adult hippocampus, however are not discussed in the current article [3] [4][5] .

Astrocyte reprogramming (addition edit): One of the more important topics that we wish to add to this article and we believe is of utmost importance is the topic of adult neurogenesis by epigenetic reprogramming of astrocytes and other glial cells, in addition to pluripotent neural progenitor cells. This topic is only briefly discussed under the topic of “embryonic neurogenesis” and subtopic “DNA methylation,” but focuses only on the programming of astrocytes in embryonic cells, not in their ‘reprogramming’ into neuronal cells in adult neurogenesis. [6]This inclusion should serve to highlight current knowledge within the field of this topic, and improve its overall profundity.

Epigenetic misregulation dysregulation and neurological disorders: Furthermore, we would also like to add a few more subtopics under "epigenetic misregulation and neurological disorders." The topic itself mentions epigenetic effects of Parkinson's disease, Alzheimer's disease, schizophrenia and bipolar disease, however only contains one subtopic discussing Alzheimer's disease alone. We believe that it would be beneficial for the depth of the article to include information regarding the epigenetic effects of the other diseases as well and provide subtopics for each, utilizing other sources which were note included.

For the epigenetic effects of Parkinson’s disease (PD) section, we would like to add more about how epigenetic modulation is a factor that is responsible for inducing gene expression, which in turn then regulates our development, cellular fate commitment, and adaptations to the environment-and how imbalances or changes in these areas can lead to the onset of PD: “Epigenetic modulation of gene expression by environmental factors is emerging as an important mechanism in PD and in other neurodegenerative disorders (such as the ones mentioned above). Thus, epigenetic mechanisms, such as DNA methylation, histone modifications and altered microRNA expression, have been under intense investigation due to their possible involvement in PD.”

  1. for example, we could discuss how studies have shown that there are significant differences in methylation levels between healthy individuals and those with PD, which may suggest that a lack of methylation may influence or is at the very least associated with Parkinson’s, “In agreement with results in brain tissue, these studies reported a significant decrease in methylation of the SNCA promoter.”[7]
  2. beyond this, we could also discuss how PD is influenced by other epigenetic factors such as histone modifications and miRNAs.

Bipolar disorders are both highly complex and heritable, which makes it an interesting disorder to examine for epigenetic modifications. DNA methylation, DNA hydroxymethylation, and histone modifications are all capable of contributing to the formation of bipolar disorder.  For example, studies of monozygotic twins revealed that individuals with bipolar disorder had lower methylation of the peptidylprolyl isomerase E-like (PPIEL) gene, which can be attributed to the dopamine transmission. Moreover, therapeutic interventions such as engineered transcription factors could modify chromatin structure. DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors could possibly reverse epigenetic modifications in order to therapeutically address bipolar disorder.[8]


Edit Key:

All edits and additions are bolded and italicized.

Please get rid of the outline, but please also keep the edit key.


Article body

Embryonic neurogenesis

Histone modifications (cleanup edit)

Neural stem cells generate the cortex in a precise "inside out" manner with carefully controlled timing mechanisms*1*. Early born neurons form deep layers in the cortex while newer born form the upper layers. This timing program is seen in vitro as well as in vivo. Histone methylation has been shown to be one of the epigenetic regulatory mechanisms which alters the proportionate production of deep layer and upper layer neurons. Specifically, deletion of a portion of the PRC2 complex, Ezh2, encoding histone methyltransferase led to a twofold reduction of POU3F2/BRN2-expressing and SATB2 expressing upper layer neurons without affecting the number of neurons in layer V and VI *2* *3*. Similarly, histone acetylation through histone deacetylase (HDAC) inhibitor valproic acid, an epilepsy therapeutic, in mouse embryonic stem cell (ESC) derived neural progenitors not only induces neuronal differentiation, but also selectively enriched the upper layer neuronal population. As such, it has been proposed that HDAC inhibition promotes the progression of neuronal differentiation, leading to a fate-switch from deep-layer producing progenitors into upper-layer progenitors. However, the reasons behind this selective differentiation and timing control as a result of HDAC inhibition are not yet fully understood.

What's the mechanism for your proposed edit? What happens to development when there are fewer of these types of neurons? 

*1* This sentence is pretty awkward. "Generate"? in place of "develops"? Terrible.

*2* Prior sentences talk about normal development and this sentence talks about development in a mutant. People will assume that this sentence is part of normal development and that deletion of part of PRC2 is a normal developmental process. This is what you led them to think. Please fix.

*3* There is a lot more that should be cleaned up about this paragraph. In general as constructed I think that the separation between the description of normal development and the mutant phenotype is nonexistant. Really you just need some transition phrases here and there that help the reader. For instance, you could rewrite sentence 3 like this: Mutant analysis has shown that histone methylation modulates the production of deep layer and upper layer neurons.

Adult neurogenesis


Astrocyte reprogramming: (addition)

Astrocytes are specialized glial cells that vastly outnumber neurons in the adult brain, due to their ability to multiply as needed to sustain proper levels for brain function through multiple functions, including blood brain barrier control, supporting synapses as well as axon pathfinding. [9] <- there are a lot of residues Unlike neurons, these specialized glial cells are able to alter their cell fate and “dedifferentiate,” in large part due to epigenetic factors, into other cell types prior to maturation. This dedifferentiation allows astrocytes to potentially reach a different cell fate entirely, which can lead to their consequent differentiation and conversion from glial cells into neurons in the adult brain.[6] Prior to complete maturation while dedifferentiation is still possible, the expression of genes Mash1, NeuroG1 and NeuroG2 can allow for reprogramming of astrocytes into neurons. [10] In addition to the expression of these genes in brain cells, multiple epigenetic factors play a role in these gene’s expression patterns. An up-regulation of acetylation at H3K9K14 <- is this acetylation at both these residues? adjacent to both NeuroG1 and NeuroG2 genes has been shown to accompany astrocyte dedifferentiation, and further silencing of methylation mechanisms, which themselves are involved in silencing expression, inhibits the progenitor cells of astrocytes from differentiating back to their original fate as glial cells.[11] Once in this inhibited stage, expression of the gene NeuroD4 in these specified glial cells has been shown to lead to neuronal formation, and thus neurogenesis, from the dedifferentiated astrocytes in adult mammalian brains.[6]

I'm a little confused about the timing of things here. It initially sounds like astrocytes can be reprogrammed at any point, but then later it's written as if this has to happen before final maturation steps. Can you clear up some of the timing of when this happens and also when astrocytes are committed to their cell fate (if at all)?

Expand on the epigenetic aspect here a little more.

Histone modification (edit)

Histone acetylation, deacetylation, as well as the inhibition of histone deacetylation mechanisms also play large roles in the proliferation and self-renewal of post-natal neural stem cells, in contrasting ways. <- I'm not sure what you mean by "in contrasting ways" Neural-expressed HDACs interact with Tlx, an essential neural stem cell regulator, to suppress TLX target genes. This includes the cyclin-dependent kinase inhibitor P21 and the tumor suppressor gene Pten to promote neural stem cell proliferation.[12] The most prominently studied and well-understood regulators of chromatin remodeling, which play an important role in adult neurogenesis are histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs add acetyl groups to nucleosomes, while HDACs remove them. The acetylation of histones leads to decreased condensation of the nucleosomes to target DNA, and increases the likelihood that gene expression may occur by freeing up the DNA targets to bind to their respective transcriptional factors. This process is involved in neural proliferation regulation, as different neuronal cell genes are expressed and repressed. Deacetylation of histones leads to the reverse, and increases the likelihood for the repression of gene expression. HDAC inhibitors (HDACi), such as valproic acid (VPA) and trichostatin A can promote proliferation of adult neurogenesis through the reversal of HDAC activity, inducing differentiation of adult progenitor cells.[1] <- It feels like this should come before the second sentence of the paragraph since it starts to discuss HDACs -- it would make sense to have this background info before the details. It might also be good to split this up into a background paragraph and a paragraph talking about the role of histone modifications in neurogenesis. Inhibition of HDACS by the antiepileptic drug valproic acid induces neuronal differentiation as in embryonic neurogenesis, but also inhibits glial cell differentiation of adult neural stem cells. This is likely mediated through upregulation of neuronal specific genes such as the neurogeneic basic helix-loop-helix transcription factors NEUROD, NEUROGENENIN1, and Math1. Conditional loss of HDAC1, HDAC2 in neural progenitor cells prevented them from differentiating into neurons and their loss in oligodendrytic progenitor cells disrupted oligodendrocyte formations, suggesting that histone deacetlyation plays important but varying roles in different stages of neuronal development. [12]

This section is titled "histone modifications" but only really focuses on histone acetylation, specifically the role of HDACs. Can you expand this a little more? Also, the model you're working with of histone acetylation making chromatin more accessible is pretty simplistic - consider the other things histone acetylation does like recruitment of chromatin proteins, reinforcement and expansion of acetylation, etc.

miRNAs (edit)

MicroRNAs (miRNAs) are small noncoding RNAs that play a significant role in eukaryotic epigenetic regulation. miRNAs function to modulate protein expression levels of their mRNA targets without affecting the sequences of the genes of interest. While miRNAs play a large role in the modulation of epigenetic mechanisms, they are also modified and regulated by other epigenetic factors including DNA methylation, histone modifications and other RNA modifications.[13] Together, miRNAs create an epigenetic feedback loop with other epigenetic factors to affect the expression levels of specific genes. A number of specific miRNAs have been implicated as agents of epigenetic regulation in adult neurogenesis. miR-9 targets the nuclear receptor TLX in adult neurogenesis to promote neural differentiation and inhibit neural stem cell proliferation. It also influences neuronal subtype specification and regulates axonal growth, branching, and targeting in the central nervous system through interactions with HES1, a neural stem cell homeostasis molecule. miR-124 promotes cell cycle exit and neuronal differentiation in adult neurogenesis. Mouse studies have shown that ectopic expression of miR-124 showed premature neural progenitor cell differentiation and exhaustion in the subventricular zone. In addition to miR-9 and miR-124, other miRNAs play essential roles in regulation of adult neurogenesis. miR-137, miR-184 and miR-195 regulate adult neural stem cell proliferation, with their over-expression leading to up-regulated proliferation while their down-regulation leads to a decrease in neuronal proliferation. [3] Methyl-CpG binding protein 1 (MBD1) represses miR-184, which is a microRNA responsible for proliferation of adult neural stem/progenitor cells (aNSCs) along with the inhibition of differentiating these cells. miR-184 regulates embryonic brain development by binding to the mRNA for the Numblike (Numbl) protein and altering its expression. MBD1, Numbl, and miR-184 all work together to regulate the proliferation and differentiation of aNSCs. [4] In addition, miR-195 works closely with MBD1 to regulate aNSC proliferation and differentiation. mIR-194 and MBD1 form a negative regulatory loop in aNSCs and work to repress the expression of each other. Inhibition of miR-195 promotes aNSC differentiation. Once differentiation has occurred, levels of miR-195 decreases. [5]

Might be a good idea to break up this paragraph too.

Epigenetic dysregulation and neurological disorders (section addition)

Epigenetic dysregulation, or alterations on epigenomic machinery, can cause DNA methylation and histone acetylation processes to go rogue. The epigenetic machinery influence neural differentiation regulation (i.e. neurogenesis) [14] and are also involved in processes related to memory consolidation and learning in healthy individuals.[15] As aging is the main risk for many neurological disorders, epigenetic dysregulation can in turn lead to alterations on the transcriptional level of genes involved in the pathogenesis of neural degenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, schizophrenia, and bipolar disease.[12][16]

Can you draw a general link between aging and altered epigenetic mechanisms? Feels like that would help strengthen your claim about aging risk and epigenetic mechanisms.

Huntington’s disease (addition)

Histone acetylation has received increasing support over the years as a proposed mechanism for the dysregulation of HD.[17]

Preclinical studies have been performed using various HDACi’s [such as suberoxylanilide hydroxamic acid (SAHA), Trichostatin A (TSA), phenylbutyrate, and sodium butyrate (NaB)] that target HDACI and HDACII. Although these inhibitors improve some phenotypes of HD in mice, such as neuropathology and motor function, the beneficial effects do not provide a clear indication of the necessity of an increase in histone acetylation. However, inactivation of a target of SAHA, Hdac 4, alleviates neurodegenerative complications in mice with HD through a transcription-independent mechanism which acts upon mutant Htt aggregation processes-which may indicate that there is a mechanism involving non-histone proteins. <- This is super important! Say more about this mechanism, especially since almost all of your discussion of HDACs and histone acetylation has been focused on transcription, mentioning a transcription-independent mechanism and then not explaining it is going to bug your readers (like it did me).You pique our curiosity and then leave us hanging!

HDACi treatment still does not have clear results in regards to the restoration of neuronal identity genes. However clinical studies using HDACi are currently ongoing and the results are pending, with the Phase II studies showing promise for safe and tolerable use of several compounds such as phenylbutyrate.

Non-histone-mediated beneficial effects of HDACi have also been documented in models of Parkinson disease, suggesting common mechanisms between several neurodegenerative diseases.

Parkinson’s disease (addition)

DNA methylation analysis showed that there is significant dysregulation of methylation on CpG islands on patients with PD when compared to healthy individuals. Although this was genome-wide, this also occurred on many PD risk genes.[7]

Mitochondrial DNA methylation has also been shown to have variance over time due to age variance. As mitochondria plays a role in the development of the PD, further research into the area will help uncover any implications that mitochondrial DNA methylation plays in the pathogenesis of PD.

Can you draw any stronger of a link here? What does methylation of mitochondrial DNA do (as far as I know mtDNA doesn't really get packaged into chromatin)? Would this methylation reasonably affect mitochondrial function in a similar manner to what's seen in PD?

The use of dopaminergic neurons that have been isolated from the PD patients indicated that there were increases in acetylation (at H2A, H3 and H4) when compared to the age-control group.[7] Beyond this, HDAC levels are reduced in 1-methyl-4-phenylpyridinium (MPP+)-treated cells and in MPTP-treated mouse brains, as well as in midbrain samples from patients with PD. <- what's this treatment? what does it do, and why do you see these changes? These results point towards the stress of  histone modifications in regards to chromatin remodeling and its implication in the pathogenesis of PD.

miRNAs are also emerging as relevant contributors to neurodegeneration in PD. In particular, the frontal cortex PD patients have shown higher levels of LRRK2 and lower levels of miR-205 when compared to healthy individuals. Connecting this to the findings of miR-205’s ability to bind to the 3′ UTR of LRRK2 mRNA and suppress expression, as well as miR-205’s prevention of defects after introduction to a R1441G LRRK2 mutation, these results point towards miR-205 and its regulatory role in LRRK2 expression-which in turn suggest a regulatory role in the pathogenesis of PD.

You don't link to this the HDACi effects you mentioned in the HD section. I think you should expand on that link since you claim it exists.

Bipolar Disorder (addition)

Bipolar disorders are both highly complex and heritable, which makes it an interesting disorder to examine for epigenetic modifications. DNA methylation, DNA hydroxymethylation, and histone modifications are all capable of contributing to the formation of bipolar disorder.  

For example, studies of monozygotic twins revealed that individuals with bipolar disorder had lower methylation of the peptidylprolyl isomerase E-like (PPIEL) gene, which can be attributed to the dopamine transmission. The studies indicated that hypermethylation of SLC6A4, a serotinin transporter gene, is also involved with bipolar disorder. The methylation of CpG regions are relevant to bipolar disorders. Patients with bipolar disorder showed lower methylation levels for the CpG region of the KCNQ3 gene, which is responsible for the voltage-gated K+ channel. Childhood maltreatment contributed to the methylation status of CpG2 III of 5-hydroxytryptamine 3A, which alters how maltreatment affects bipolar disorder. [8]

Explain these mechanisms a little more. Why are these changes in methylation associated with bipolar? What causes them?

Moreover, therapeutic interventions such as engineered transcription factors could modify chromatin structure. DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors could possibly reverse epigenetic modifications in order to therapeutically address bipolar disorder.

Dive into these treatments a little more. I think this comment applies for all the sections here.

~~General comments~~

This looks to be in pretty good shape. I think just expanding on a lot of these topics is the focus at this point. I don't really have much more to say than to think about mechanisms more and the structures of these paragraphs.


References

  1. ^ a b Hsieh, Jenny; Zhao, Xinyu (2016). "Genetics and Epigenetics in Adult Neurogenesis". Cold Spring Harbor Perspectives in Biology. 8 (6): a018911. doi:10.1101/cshperspect.a018911. ISSN 1943-0264. PMC 4888816. PMID 27143699.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ Jobe, Emily M.; McQuate, Andrea L.; Zhao, Xinyu (2012). "Crosstalk among Epigenetic Pathways Regulates Neurogenesis". Frontiers in Neuroscience. 6. doi:10.3389/fnins.2012.00059. ISSN 1662-4548. PMC 3347638. PMID 22586361.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  3. ^ a b Szulwach, Keith E.; Li, Xuekun; Smrt, Richard D.; Li, Yujing; Luo, Yuping; Lin, Li; Santistevan, Nicholas J.; Li, Wendi; Zhao, Xinyu; Jin, Peng (2010-04-05). "Cross talk between microRNA and epigenetic regulation in adult neurogenesis". Journal of Cell Biology. 189 (1): 127–141. doi:10.1083/jcb.200908151. ISSN 1540-8140. PMC 2854370. PMID 20368621.{{cite journal}}: CS1 maint: PMC format (link)
  4. ^ a b Liu, Changmei; Teng, Zhao-Qian; Santistevan, Nicholas J.; Szulwach, Keith E.; Guo, Weixiang; Jin, Peng; Zhao, Xinyu (2010-05). "Epigenetic Regulation of miR-184 by MBD1 Governs Neural Stem Cell Proliferation and Differentiation". Cell Stem Cell. 6 (5): 433–444. doi:10.1016/j.stem.2010.02.017. PMC 2867837. PMID 20452318. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  5. ^ a b Liu, Changmei; Teng, Zhao-Qian; McQuate, Andrea L.; Jobe, Emily M.; Christ, Christa C.; von Hoyningen-Huene, Sergei J.; Reyes, Marie D.; Polich, Eric D.; Xing, Yina; Li, Yue; Guo, Weixiang (2013-01-17). Van Wijnen, Andre (ed.). "An Epigenetic Feedback Regulatory Loop Involving MicroRNA-195 and MBD1 Governs Neural Stem Cell Differentiation". PLoS ONE. 8 (1): e51436. doi:10.1371/journal.pone.0051436. ISSN 1932-6203. PMC 3547917. PMID 23349673.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  6. ^ a b c Griffiths, BrianB; Bhutani, Anvee; Stary, CreedM (2020). "Adult neurogenesis from reprogrammed astrocytes". Neural Regeneration Research. 15 (6): 973. doi:10.4103/1673-5374.270292. ISSN 1673-5374. PMC 7034263. PMID 31823866.{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
  7. ^ a b c Pavlou, Maria Angeliki S.; Outeiro, Tiago Fleming (2017), Delgado-Morales, Raul (ed.), "Epigenetics in Parkinson's Disease", Neuroepigenomics in Aging and Disease, Advances in Experimental Medicine and Biology, Cham: Springer International Publishing, pp. 363–390, doi:10.1007/978-3-319-53889-1_19, ISBN 978-3-319-53889-1, retrieved 2022-03-10
  8. ^ a b Ludwig, B; Dwivedi, Y (2016). "Dissecting bipolar disorder complexity through epigenomic approach". Molecular Psychiatry. 21 (11): 1490–1498. doi:10.1038/mp.2016.123. ISSN 1359-4184. PMC 5071130. PMID 27480490.
  9. ^ Blackburn, Daniel; Sargsyan, Siranush; Monk, Peter N.; Shaw, Pamela J. (2009). "Astrocyte function and role in motor neuron disease: A future therapeutic target?". Glia. 57 (12): 1251–1264. doi:10.1002/glia.20848.
  10. ^ Berninger, B.; Costa, M. R.; Koch, U.; Schroeder, T.; Sutor, B.; Grothe, B.; Gotz, M. (2007-08-08). "Functional Properties of Neurons Derived from In Vitro Reprogrammed Postnatal Astroglia". Journal of Neuroscience. 27 (32): 8654–8664. doi:10.1523/JNEUROSCI.1615-07.2007. ISSN 0270-6474. PMC 6672931. PMID 17687043.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ Bulstrode, Harry; Johnstone, Ewan; Marques-Torrejon, Maria Angeles; Ferguson, Kirsty M.; Bressan, Raul Bardini; Blin, Carla; Grant, Vivien; Gogolok, Sabine; Gangoso, Ester; Gagrica, Sladjana; Ender, Christine (2017-04-15). "Elevated FOXG1 and SOX2 in glioblastoma enforces neural stem cell identity through transcriptional control of cell cycle and epigenetic regulators". Genes & Development. 31 (8): 757–773. doi:10.1101/gad.293027.116. ISSN 0890-9369. PMC 5435889. PMID 28465359.{{cite journal}}: CS1 maint: PMC format (link)
  12. ^ a b c Hu, Xiao-Ling; Wang, Yuping; Shen, Qin (2012-4). "Epigenetic control on cell fate choice in neural stem cells". Protein & Cell. 3 (4): 278–290. doi:10.1007/s13238-012-2916-6. ISSN 1674-800X. PMC 4729703. PMID 22549586. {{cite journal}}: Check date values in: |date= (help)
  13. ^ Yao, Qian; Chen, Yuqi; Zhou, Xiang (2019-08). "The roles of microRNAs in epigenetic regulation". Current Opinion in Chemical Biology. 51: 11–17. doi:10.1016/j.cbpa.2019.01.024. {{cite journal}}: Check date values in: |date= (help)
  14. ^ Yao, Bing; Christian, Kimberly M.; He, Chuan; Jin, Peng; Ming, Guo-li; Song, Hongjun (2016-9). "Epigenetic mechanisms in neurogenesis". Nature reviews. Neuroscience. 17 (9): 537–549. doi:10.1038/nrn.2016.70. ISSN 1471-003X. PMC 5610421. PMID 27334043. {{cite journal}}: Check date values in: |date= (help)
  15. ^ Delgado-Morales, Raúl; Agís-Balboa, Roberto Carlos; Esteller, Manel; Berdasco, María (2017-06-29). "Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders". Clinical Epigenetics. 9 (1): 67. doi:10.1186/s13148-017-0365-z. ISSN 1868-7083.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  16. ^ Dempster, Emma L.; Pidsley, Ruth; Schalkwyk, Leonard C.; Owens, Sheena; Georgiades, Anna; Kane, Fergus; Kalidindi, Sridevi; Picchioni, Marco; Kravariti, Eugenia; Toulopoulou, Timothea; Murray, Robin M. (2011-12-15). "Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder". Human Molecular Genetics. 20 (24): 4786–4796. doi:10.1093/hmg/ddr416. ISSN 0964-6906. PMC 3221539. PMID 21908516.
  17. ^ Francelle, Laetitia; Lotz, Caroline; Outeiro, Tiago; Brouillet, Emmanuel; Merienne, Karine (2017-01-30). "Contribution of Neuroepigenetics to Huntington's Disease". Frontiers in Human Neuroscience. 11: 17. doi:10.3389/fnhum.2017.00017. ISSN 1662-5161. PMC 5276857. PMID 28194101.{{cite journal}}: CS1 maint: unflagged free DOI (link)
Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=User:AAR3643/Epigenetic_regulation_of_neurogenesis&oldid=1085324160"