View source for Histone deacetylase 2

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Histone deacetylase 2''' ('''HDAC2''') is an [[enzyme]] that in humans is encoded by the ''HDAC2'' [[gene]].<ref name="pmid97820973">{{cite journal | vauthors = Betz R, Gray SG, Ekström C, Larsson C, Ekström TJ | title = Human histone deacetylase 2, HDAC2 (Human RPD3), is localized to 6q21 by radiation hybrid mapping | journal = Genomics | volume = 52 | issue = 2 | pages = 245–246 | date = September 1998 | pmid = 9782097 | doi = 10.1006/geno.1998.5435 }}</ref>  It belongs to the [[histone deacetylase]] class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core [[histone]]s (H2A, H2B, H3, and H4). As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.<ref>{{Cite web|url=https://www.proteinatlas.org/ENSG00000196591-HDAC2/tissue|title=Tissue expression of HDAC2 - Summary - The Human Protein Atlas|website=www.proteinatlas.org|access-date=2019-03-14}}</ref>

Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by [[Casein kinase 2|protein kinase 2 (CK2)]] and [[Protein phosphatase 1|protein phosphatase 1 (PP1)]], but biochemical analysis suggests its regulation is more complex (evinced by the coexistence of HDAC1 and HDAC2 in three distinct protein complexes).<ref>{{cite journal | vauthors = Seto E, Yoshida M | title = Erasers of histone acetylation: the histone deacetylase enzymes | journal = Cold Spring Harbor Perspectives in Biology | volume = 6 | issue = 4 | pages = a018713 | date = April 2014 | pmid = 24691964 | pmc = 3970420 | doi = 10.1101/cshperspect.a018713 }}</ref> Essentially, the mechanism by which HDAC2 is regulated is still unclear by virtue of its various interactions, though a mechanism involving p300/CBP-associated factor and HDAC5 has been proposed in the context of cardiac reprogramming.<ref name=":0">{{cite journal | vauthors = Eom GH, Nam YS, Oh JG, Choe N, Min HK, Yoo EK, Kang G, Nguyen VH, Min JJ, Kim JK, Lee IK, Bassel-Duby R, Olson EN, Park WJ, Kook H | display-authors = 6 | title = Regulation of acetylation of histone deacetylase 2 by p300/CBP-associated factor/histone deacetylase 5 in the development of cardiac hypertrophy | journal = Circulation Research | volume = 114 | issue = 7 | pages = 1133–1143 | date = March 2014 | pmid = 24526703 | doi = 10.1161/CIRCRESAHA.114.303429 | doi-access = free }}</ref>

Generally, HDAC2 is considered a putative target for the treatment for a variety of diseases, due to its involvement in cell cycle progression. Specifically, HDAC2 has been shown to play a role in [[cardiac hypertrophy]],<ref name=":0" /> [[Alzheimer's disease]],<ref name=":1">{{cite journal | vauthors = Choubey SK, Jeyakanthan J | title = Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor - a novel target to prevent Alzheimer's disease | journal = Journal of Receptor and Signal Transduction Research | volume = 38 | issue = 3 | pages = 266–278 | date = June 2018 | pmid = 29932788 | doi = 10.1080/10799893.2018.1476541 | s2cid = 49385438 }}</ref> [[Parkinson's disease]],<ref name=":2">{{cite journal | vauthors = Tan Y, Delvaux E, Nolz J, Coleman PD, Chen S, Mastroeni D | title = Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease | journal = Neurobiology of Aging | volume = 68 | pages = 134–141 | date = August 2018 | pmid = 29803514 | doi = 10.1016/j.neurobiolaging.2018.02.018 | s2cid = 44067840 }}</ref> [[acute myeloid leukemia]] (AML),<ref>{{cite journal | vauthors = Lei L, Xia S, Liu D, Li X, Feng J, Zhu Y, Hu J, Xia L, Guo L, Chen F, Cheng H, Chen K, Hu H, Chen X, Li F, Zhong S, Mittal N, Yang G, Qian Z, Han L, He C | display-authors = 6 | title = Genome-wide characterization of lncRNAs in acute myeloid leukemia | journal = Briefings in Bioinformatics | volume = 19 | issue = 4 | pages = 627–635 | date = July 2018 | pmid = 28203711 | pmc = 6355113 | doi = 10.1093/bib/bbx007 }}</ref> [[osteosarcoma]],<ref>{{cite journal | vauthors = La Noce M, Paino F, Mele L, Papaccio G, Regad T, Lombardi A, Papaccio F, Desiderio V, Tirino V | display-authors = 6 | title = HDAC2 depletion promotes osteosarcoma's stemness both in vitro and in vivo: a study on a putative new target for CSCs directed therapy | journal = Journal of Experimental & Clinical Cancer Research | volume = 37 | issue = 1 | pages = 296 | date = December 2018 | pmid = 30509303 | pmc = 6276256 | doi = 10.1186/s13046-018-0978-x | doi-access = free }}</ref> and [[stomach cancer]].<ref>{{cite journal | vauthors = Wei J, Wang Z, Wang Z, Yang Y, Fu C, Zhu J, Jiang D | title = MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer | journal = BioMed Research International | volume = 2017 | pages = 5348490 | date = 2017 | pmid = 29333444 | pmc = 5733238 | doi = 10.1155/2017/5348490 | doi-access = free }}</ref>

== Structure and mechanism ==
[[File:HDAC2_attacking_lysine_residue.pdf|alt=|left|thumb|311x311px|This image shows the structure of the HDAC2 enzyme. The two consecutive benzene rings form the foot pocket, where as the single benzene rings forms the lipophilic tube.]]
HDAC2 belongs to the first class of histone deactylases. The active site of HDAC2 contains a Zn<sup>2+</sup> ion coordinated to the carbonyl group of a lysine substrate and a water molecule. The metallic ion facilitates the nucleophilic attack of the carbonyl group by a coordinated water molecule, leading to the formation of a tetrahedral intermediate. This intermediate is momentarily stabilized by hydrogen bond interactions and metal coordination, until it ultimately  collapses resulting in the deacetylation of the lysine residue.<ref>{{cite journal |author4-link=David W. Christianson | vauthors = Lombardi PM, Cole KE, Dowling DP, Christianson DW | title = Structure, mechanism, and inhibition of histone deacetylases and related metalloenzymes | journal = Current Opinion in Structural Biology | volume = 21 | issue = 6 | pages = 735–743 | date = December 2011 | pmid = 21872466 | pmc = 3232309 | doi = 10.1016/j.sbi.2011.08.004 }}</ref>

The HDAC2 active site consists of a lipophilic tube which leads from the surface to the catalytic center, and a 'foot pocket' containing mostly water molecules. The active site is connected to Gly154, Phe155, His183, Phe210, and Leu276. The footpocket is connected to Tyr29, Met35, Phe114, and Leu144.<ref name="pmid20392638">{{cite journal | vauthors = Bressi JC, Jennings AJ, Skene R, Wu Y, Melkus R, De Jong R, O'Connell S, Grimshaw CE, Navre M, Gangloff AR | display-authors = 6 | title = Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl)benzamides | journal = Bioorganic & Medicinal Chemistry Letters | volume = 20 | issue = 10 | pages = 3142–3145 | date = May 2010 | pmid = 20392638 | doi = 10.1016/j.bmcl.2010.03.091 }}</ref>

== Function ==
This gene product belongs to the [[histone deacetylase]] family. Histone deacetylases act via the formation of large multiprotein complexes and are responsible for the deacetylation of lysine residues on the N-terminal region of the core histones (H2A, H2B, H3 and H4). This protein also forms transcriptional repressor complexes by associating with many different proteins, including YY1, a mammalian zinc-finger transcription factor. Thus, it plays an important role in transcriptional regulation, cell cycle progression and developmental events.<ref name="entrez3">{{cite web|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3066|title=Entrez Gene: HDAC2 histone deacetylase 2}}</ref>

== Disease relevance ==

=== Cardiac hypertrophy ===
HDAC2 has been shown to play a role in the regulatory pathway of cardiac hypertrophy. Deficiencies in HDAC2 were shown to mitigate cardiac hypertrophy in hearts exposed to hypertrophic stimuli. However, in HDAC2 transgenic mice with inactivated glycogen synthase kinase 3beta (Gsk3beta), hypertrophy was observed at a higher frequency. In mice with activated Gsk3beta enzymes and HDAC2 deficiencies, sensitivity to hypertrophic stimulus was observed at a higher rate. The results suggest regulatory roles of HDAC2 and GSk3beta.<ref>{{cite journal | vauthors = Trivedi CM, Luo Y, Yin Z, Zhang M, Zhu W, Wang T, Floss T, Goettlicher M, Noppinger PR, Wurst W, Ferrari VA, Abrams CS, Gruber PJ, Epstein JA | display-authors = 6 | title = Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity | journal = Nature Medicine | volume = 13 | issue = 3 | pages = 324–331 | date = March 2007 | pmid = 17322895 | doi = 10.1038/nm1552 | s2cid = 33021404 }}</ref>[[File:HDAC2_Chem_183.pdf|alt=|thumb|302x302px|The HDAC2 enzyme attacking a lysine residue.]]Mechanisms by which HDAC2 responds to hypertrophic stress have been proposed, though no general consensus has been met. One suggested mechanism puts forth [[casein kinase]] dependent [[phosphorylation]] of HDAC2, while a more recent mechanism suggests acetylation regulated by p300/CBP-associated factor and [[HDAC5]].<ref name=":0" />

=== Alzheimer's disease ===
It has been found that patients with Alzheimer's disease experience a decrease in the expression of neuronal genes.<ref name="pmid21821124">{{cite journal | vauthors = Ginsberg SD, Alldred MJ, Che S | title = Gene expression levels assessed by CA1 pyramidal neuron and regional hippocampal dissections in Alzheimer's disease | journal = Neurobiology of Disease | volume = 45 | issue = 1 | pages = 99–107 | date = January 2012 | pmid = 21821124 | pmc = 3220746 | doi = 10.1016/j.nbd.2011.07.013 }}</ref> Furthermore, a recent study found that inhibition of HDAC2 via c-Abl by [[Tyrosine kinase|tyrosine]] phosphorylation prevented cognitive and behavioral impairments in mice with Alzheimer's disease.<ref>{{cite journal | vauthors = Gonzalez-Zuñiga M, Contreras PS, Estrada LD, Chamorro D, Villagra A, Zanlungo S, Seto E, Alvarez AR | display-authors = 6 | title = c-Abl stabilizes HDAC2 levels by tyrosine phosphorylation repressing neuronal gene expression in Alzheimer's disease | journal = Molecular Cell | volume = 56 | issue = 1 | pages = 163–173 | date = October 2014 | pmid = 25219501 | doi = 10.1016/j.molcel.2014.08.013 | doi-access = free }}</ref> The results of the study support the role of c-Abl and HDAC2 in the signaling pathway of gene expression in patients with Alzheimer's disease.  Currently, efforts to synthesize an HDAC2 inhibitor for the treatment of Alzheimer's disease are based on a [[pharmacophore]] with four features: one hydrogen bond acceptor, one hydrogen bond donor, and two aromatic rings.<ref name=":1" />

=== Parkinson's disease ===
HDAC inhibitors have been regarded as a potential treatment of neurodegenerative diseases, such as [[Parkinson's disease]]. Parkinson's disease is usually accompanied by an increase in the number of microglial proteins in the [[substantia nigra]] of the brain. In vivo evidence has shown a correlation between the number of [[microglia]]l proteins and the [[upregulation]] of HDAC2.<ref name=":2" /> It is thought therefore that HDAC2 inhibitors could be effective in treating microglial-initiated loss of dopaminergic neurons in the brain.

=== Cancer therapy ===
The role of HDAC2 in various forms of cancer such as osteosarcoma, gastric cancer, and acute myeloid leukemia have been studied. A recent study discovered decreased metastasis formation in mouse models that develop pancreatic cancer when the murine ortholog ''Hdac2'' was genetically depleted.<ref>{{cite journal | vauthors = Krauß L, Urban BC, Hastreiter S, Schneider C, Wenzel P, Hassan Z, Wirth M, Lankes K, Terrasi A, Klement C, Cernilogar FM, Öllinger R, de Andrade Krätzig N, Engleitner T, Schmid RM, Steiger K, Rad R, Krämer OH, Reichert M, Schotta G, Saur D, Schneider G | display-authors = 6 | title = HDAC2 Facilitates Pancreatic Cancer Metastasis | journal = Cancer Research | volume = 82 | issue = 4 | pages = 695–707 | date = February 2022 | pmid = 34903606 | doi = 10.1158/0008-5472.CAN-20-3209 | pmc = 9359718 | s2cid = 245193477 | doi-access = free }}</ref> Current research is focused on creating inhibitors that decrease the upregulation of HDAC2. 

=== Anti-influenza virus factor ===
HDAC2 plays a role in regulating the Signal Transducer and Activator of Transcription I (STAT1) and interferon-stimulated gene such as viperin. This shows that HDAC2 might be a component of cellular innate antiviral response. To circumvent the anti-viral potential, influenza A virus dysregulates HDAC2 by inducing its degradation by proteasomal degradation.<ref>{{cite journal | vauthors = Nagesh PT, Hussain M, Galvin HD, Husain M | title = Histone Deacetylase 2 Is a Component of Influenza A Virus-Induced Host Antiviral Response | journal = Frontiers in Microbiology | volume = 8 | pages = 1315 | date = 2017 | pmid = 28769891 | pmc = 5511851 | doi = 10.3389/fmicb.2017.01315 | doi-access = free }}</ref>

== Interactions ==

Histone deacetylase 2 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[Ataxia telangiectasia and Rad3 related]],<ref name = pmid10545197/> 
* [[BUB3]],<ref name = pmid15388328/> 
* [[CDC20]],<ref name = pmid15388328>{{cite journal | vauthors = Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW | display-authors = 6 | title = WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase | journal = FEBS Letters | volume = 575 | issue = 1–3 | pages = 23–29 | date = September 2004 | pmid = 15388328 | doi = 10.1016/j.febslet.2004.07.089 | s2cid = 21762011 | doi-access = free }}</ref> 
* [[CDH1 (gene)|CDH1]],<ref name = pmid15388328/> 
* [[CHD3]],<ref name = pmid12493763>{{cite journal | vauthors = Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R | title = A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes | journal = The Journal of Biological Chemistry | volume = 278 | issue = 9 | pages = 7234–7239 | date = February 2003 | pmid = 12493763 | doi = 10.1074/jbc.M208992200 | doi-access =  free}}</ref><ref name = pmid9804427>{{cite journal | vauthors = Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL | title = Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex | journal = Nature | volume = 395 | issue = 6705 | pages = 917–921 | date = October 1998 | pmid = 9804427 | doi = 10.1038/27699 | s2cid = 4355885 | bibcode = 1998Natur.395..917T }}</ref><ref name = pmid12198550>{{cite journal | vauthors = Hakimi MA, Bochar DA, Schmiesing JA, Dong Y, Barak OG, Speicher DW, Yokomori K, Shiekhattar R | display-authors = 6 | title = A chromatin remodelling complex that loads cohesin onto human chromosomes | journal = Nature | volume = 418 | issue = 6901 | pages = 994–998 | date = August 2002 | pmid = 12198550 | doi = 10.1038/nature01024 | s2cid = 4344470 | bibcode = 2002Natur.418..994H }}</ref> 
* [[CHD4]],<ref name = pmid10545197>{{cite journal | vauthors = Schmidt DR, Schreiber SL | title = Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4 | journal = Biochemistry | volume = 38 | issue = 44 | pages = 14711–14717 | date = November 1999 | pmid = 10545197 | doi = 10.1021/bi991614n }}</ref><ref name = pmid12493763/><ref name = pmid9804427/> 
* [[DNMT1]],<ref name = pmid10888872>{{cite journal | vauthors = Rountree MR, Bachman KE, Baylin SB | title = DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci | journal = Nature Genetics | volume = 25 | issue = 3 | pages = 269–277 | date = July 2000 | pmid = 10888872 | doi = 10.1038/77023 | s2cid = 26149386 }}</ref> 
* [[EED (protein)|EED]],<ref name = pmid10581039>{{cite journal | vauthors = van der Vlag J, Otte AP | title = Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation | journal = Nature Genetics | volume = 23 | issue = 4 | pages = 474–478 | date = December 1999 | pmid = 10581039 | doi = 10.1038/70602 | s2cid = 6748531 }}</ref> 
* [[EZH2]]<ref name = pmid10581039/> and 
* [[FKBP3]],<ref name = pmid11532945>{{cite journal | vauthors = Yang WM, Yao YL, Seto E | title = The FK506-binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1 | journal = The EMBO Journal | volume = 20 | issue = 17 | pages = 4814–4825 | date = September 2001 | pmid = 11532945 | pmc = 125595 | doi = 10.1093/emboj/20.17.4814 }}</ref> 
* [[GATA4]],<ref>{{cite news |url=http://www.physorg.com/news205686730.html |title=Three-way control of fetal heart-cell proliferation could help regenerate cardiac cells |date=October 7, 2010 }}</ref>
* [[GTF2I]],<ref name = pmid12493763/><ref name = pmid12393887>{{cite journal | vauthors = Wen YD, Cress WD, Roy AL, Seto E | title = Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I | journal = The Journal of Biological Chemistry | volume = 278 | issue = 3 | pages = 1841–1847 | date = January 2003 | pmid = 12393887 | doi = 10.1074/jbc.M206528200 | doi-access = free }}</ref> 
* [[HDAC10]],<ref name = pmid11739383>{{cite journal | vauthors = Fischer DD, Cai R, Bhatia U, Asselbergs FA, Song C, Terry R, Trogani N, Widmer R, Atadja P, Cohen D | display-authors = 6 | title = Isolation and characterization of a novel class II histone deacetylase, HDAC10 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 8 | pages = 6656–6666 | date = February 2002 | pmid = 11739383 | doi = 10.1074/jbc.M108055200 | doi-access = free }}</ref> 
* [[HDAC1]],<ref name = pmid12493763/><ref name = pmid9804427/><ref name = pmid10581039/><ref name = pmid11739383/><ref name = pmid12920132/><ref name = pmid12032298/><ref name = pmid11777905/><ref name = pmid11804585>{{cite journal | vauthors = Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E | title = Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR | journal = Molecular Cell | volume = 9 | issue = 1 | pages = 45–57 | date = January 2002 | pmid = 11804585 | doi = 10.1016/s1097-2765(01)00429-4 | hdl-access = free | hdl = 11858/00-001M-0000-002C-9FF9-9 }}</ref><ref name = pmid11466315>{{cite journal | vauthors = Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E | title = Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35826–35835 | date = September 2001 | pmid = 11466315 | doi = 10.1074/jbc.M104935200 | doi-access = free }}</ref><ref name = pmid11564889>{{cite journal | vauthors = Ashburner BP, Westerheide SD, Baldwin AS | title = The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression | journal = Molecular and Cellular Biology | volume = 21 | issue = 20 | pages = 7065–7077 | date = October 2001 | pmid = 11564889 | pmc = 99882 | doi = 10.1128/MCB.21.20.7065-7077.2001 }}</ref><ref name = pmid10444591>{{cite journal | vauthors = Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D | title = Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation | journal = Genes & Development | volume = 13 | issue = 15 | pages = 1924–1935 | date = August 1999 | pmid = 10444591 | pmc = 316920 | doi = 10.1101/gad.13.15.1924 }}</ref><ref name = pmid9520398>{{cite journal | vauthors = Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL | title = A role for histone deacetylase activity in HDAC1-mediated transcriptional repression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 7 | pages = 3519–3524 | date = March 1998 | pmid = 9520398 | pmc = 19868 | doi = 10.1073/pnas.95.7.3519 | doi-access = free | bibcode = 1998PNAS...95.3519H }}</ref><ref name = pmid9150135>{{cite journal | vauthors = Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D | title = Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex | journal = Cell | volume = 89 | issue = 3 | pages = 357–364 | date = May 1997 | pmid = 9150135 | doi = 10.1016/s0092-8674(00)80216-0 | doi-access = free }}</ref> 
* [[HMG20B]],<ref name = pmid12493763/><ref name = pmid12032298/> 
* [[HSPA4]],<ref name = pmid11777905>{{cite journal | vauthors = Johnson CA, White DA, Lavender JS, O'Neill LP, Turner BM | title = Human class I histone deacetylase complexes show enhanced catalytic activity in the presence of ATP and co-immunoprecipitate with the ATP-dependent chaperone protein Hsp70 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 11 | pages = 9590–9597 | date = March 2002 | pmid = 11777905 | doi = 10.1074/jbc.M107942200 | doi-access =  free}}</ref> 
* [[Host cell factor C1]],<ref name = pmid12670868>{{cite journal | vauthors = Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W | title = Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 | journal = Genes & Development | volume = 17 | issue = 7 | pages = 896–911 | date = April 2003 | pmid = 12670868 | pmc = 196026 | doi = 10.1101/gad.252103 }}</ref> 
* [[MTA1]],<ref name = pmid12493763/><ref name = pmid12920132>{{cite journal | vauthors = Yao YL, Yang WM | title = The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity | journal = The Journal of Biological Chemistry | volume = 278 | issue = 43 | pages = 42560–42568 | date = October 2003 | pmid = 12920132 | doi = 10.1074/jbc.M302955200 | doi-access = free }}</ref><ref name = pmid11146623>{{cite journal | vauthors = Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R | display-authors = 6 | title = Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor | journal = Nature Cell Biology | volume = 3 | issue = 1 | pages = 30–37 | date = January 2001 | pmid = 11146623 | doi = 10.1038/35050532 | s2cid = 23477845 }}</ref> 
* [[MTA2]],<ref name = pmid12493763/><ref name = pmid12920132/><ref name = pmid10444591/> 
* [[MXD1]],<ref name = pmid9150134>{{cite journal | vauthors = Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN | title = Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression | journal = Cell | volume = 89 | issue = 3 | pages = 349–356 | date = May 1997 | pmid = 9150134 | doi = 10.1016/s0092-8674(00)80215-9 | s2cid = 13490886 | doi-access = free }}</ref><ref name = pmid11101889>{{cite journal | vauthors = Spronk CA, Tessari M, Kaan AM, Jansen JF, Vermeulen M, Stunnenberg HG, Vuister GW | title = The Mad1-Sin3B interaction involves a novel helical fold | journal = Nature Structural Biology | volume = 7 | issue = 12 | pages = 1100–1104 | date = December 2000 | pmid = 11101889 | doi = 10.1038/81944 | s2cid = 12451972 }}</ref> 
* [[Mad1]],<ref name = pmid15388328/> 
* [[Methyl-CpG-binding domain protein 2]],<ref name = pmid10444591/><ref name = pmid12183469>{{cite journal | vauthors = Brackertz M, Boeke J, Zhang R, Renkawitz R | title = Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 43 | pages = 40958–40966 | date = October 2002 | pmid = 12183469 | doi = 10.1074/jbc.M207467200 | doi-access = free }}</ref><ref name = pmid10471499>{{cite journal | vauthors = Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A | display-authors = 6 | title = MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex | journal = Nature Genetics | volume = 23 | issue = 1 | pages = 58–61 | date = September 1999 | pmid = 10471499 | doi = 10.1038/12659 | hdl-access = free | s2cid = 6147725 | hdl = 1842/684 }}</ref> 
* [[PHF21A]],<ref name = pmid12493763/><ref name = pmid12032298/><ref name = pmid15325272>{{cite journal | vauthors = Iwase S, Januma A, Miyamoto K, Shono N, Honda A, Yanagisawa J, Baba T | title = Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression | journal = Biochemical and Biophysical Research Communications | volume = 322 | issue = 2 | pages = 601–608 | date = September 2004 | pmid = 15325272 | doi = 10.1016/j.bbrc.2004.07.163 }}</ref> 
* [[PPP1R8]],<ref name = pmid12788942>{{cite journal | vauthors = Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M | title = The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 33 | pages = 30677–30685 | date = August 2003 | pmid = 12788942 | doi = 10.1074/jbc.M302273200 | doi-access =  free}}</ref> 
* [[RBBP4]],<ref name = pmid12493763/><ref name = pmid9804427/><ref name = pmid12943729>{{cite journal | vauthors = Zhang Y, Dufau ML | title = Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 85 | issue = 2–5 | pages = 401–414 | date = June 2003 | pmid = 12943729 | doi = 10.1016/s0960-0760(03)00230-9 | s2cid = 28512341 | url = https://zenodo.org/record/1260176 }}</ref><ref name = pmid12091390>{{cite journal | vauthors = Zhang Y, Dufau ML | title = Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 36 | pages = 33431–33438 | date = September 2002 | pmid = 12091390 | doi = 10.1074/jbc.M204417200 | doi-access = free }}</ref> 
* [[RCOR1]],<ref name = pmid12032298>{{cite journal | vauthors = Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R | title = A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 11 | pages = 7420–7425 | date = May 2002 | pmid = 12032298 | pmc = 124246 | doi = 10.1073/pnas.112008599 | doi-access = free | bibcode = 2002PNAS...99.7420H }}</ref><ref name = pmid11171972>{{cite journal | vauthors = You A, Tong JK, Grozinger CM, Schreiber SL | title = CoREST is an integral component of the CoREST- human histone deacetylase complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 4 | pages = 1454–1458 | date = February 2001 | pmid = 11171972 | pmc = 29278 | doi = 10.1073/pnas.98.4.1454 | doi-access = free | bibcode = 2001PNAS...98.1454Y }}</ref> 
* [[RELA]],<ref name = pmid12419806>{{cite journal | vauthors = Kiernan R, Brès V, Ng RW, Coudart MP, El Messaoudi S, Sardet C, Jin DY, Emiliani S, Benkirane M | display-authors = 6 | title = Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65 | journal = The Journal of Biological Chemistry | volume = 278 | issue = 4 | pages = 2758–2766 | date = January 2003 | pmid = 12419806 | doi = 10.1074/jbc.M209572200 | doi-access = free }}</ref><ref name = pmid12138131>{{cite journal | vauthors = Yu Z, Zhang W, Kone BC | title = Histone deacetylases augment cytokine induction of the iNOS gene | journal = Journal of the American Society of Nephrology | volume = 13 | issue = 8 | pages = 2009–2017 | date = August 2002 | pmid = 12138131 | doi = 10.1097/01.asn.0000024253.59665.f1 | doi-access = free }}</ref> 
* [[Retinoblastoma protein]],<ref name = pmid10490602>{{cite journal | vauthors = Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE | title = RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6632–6641 | date = October 1999 | pmid = 10490602 | pmc = 84642 | doi = 10.1128/mcb.19.10.6632 }}</ref> 
* [[SAP30]],<ref name = pmid10444591/><ref name = pmid9651585>{{cite journal | vauthors = Zhang Y, Sun ZW, Iratni R, Erdjument-Bromage H, Tempst P, Hampsey M, Reinberg D | title = SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex | journal = Molecular Cell | volume = 1 | issue = 7 | pages = 1021–1031 | date = June 1998 | pmid = 9651585 | doi = 10.1016/s1097-2765(00)80102-1 | doi-access = free }}</ref><ref name = pmid11784859>{{cite journal | vauthors = Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D | title = Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1) | journal = Molecular and Cellular Biology | volume = 22 | issue = 3 | pages = 835–848 | date = February 2002 | pmid = 11784859 | pmc = 133546 | doi = 10.1128/mcb.22.3.835-848.2002 }}</ref> 
* [[SIN3A]],<ref name = pmid12493763/><ref name = pmid9804427/><ref name = pmid9150134/><ref name = pmid12943729/><ref name = pmid12091390/><ref name = pmid12724404>{{cite journal | vauthors = Fleischer TC, Yun UJ, Ayer DE | title = Identification and characterization of three new components of the mSin3A corepressor complex | journal = Molecular and Cellular Biology | volume = 23 | issue = 10 | pages = 3456–3467 | date = May 2003 | pmid = 12724404 | pmc = 164750 | doi = 10.1128/mcb.23.10.3456-3467.2003 }}</ref><ref name = pmid12398767>{{cite journal | vauthors = Yang L, Mei Q, Zielinska-Kwiatkowska A, Matsui Y, Blackburn ML, Benedetti D, Krumm AA, Taborsky GJ, Chansky HA | display-authors = 6 | title = An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B | journal = The Biochemical Journal | volume = 369 | issue = Pt 3 | pages = 651–657 | date = February 2003 | pmid = 12398767 | pmc = 1223118 | doi = 10.1042/BJ20020854 }}</ref> 
* [[SMARCA5]],<ref name = pmid12198550/> 
* [[SNW1]],<ref name = pmid10644367>{{cite journal | vauthors = Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD | title = A role for SKIP in EBNA2 activation of CBF1-repressed promoters | journal = Journal of Virology | volume = 74 | issue = 4 | pages = 1939–1947 | date = February 2000 | pmid = 10644367 | pmc = 111672 | doi = 10.1128/jvi.74.4.1939-1947.2000 }}</ref> 
* [[SUV39H1]],<ref name = pmid11788710>{{cite journal | vauthors = Vaute O, Nicolas E, Vandel L, Trouche D | title = Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases | journal = Nucleic Acids Research | volume = 30 | issue = 2 | pages = 475–481 | date = January 2002 | pmid = 11788710 | pmc = 99834 | doi = 10.1093/nar/30.2.475 }}</ref> 
* [[Sp1 transcription factor]],<ref name = pmid12091390/><ref name = pmid12151407/><ref name = pmid12176973/> 
* [[Sp3 transcription factor]],<ref name = pmid12151407>{{cite journal | vauthors = Won J, Yim J, Kim TK | title = Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells | journal = The Journal of Biological Chemistry | volume = 277 | issue = 41 | pages = 38230–38238 | date = October 2002 | pmid = 12151407 | doi = 10.1074/jbc.M206064200 | doi-access = free }}</ref><ref name = pmid12176973>{{cite journal | vauthors = Sun JM, Chen HY, Moniwa M, Litchfield DW, Seto E, Davie JR | title = The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 39 | pages = 35783–35786 | date = September 2002 | pmid = 12176973 | doi = 10.1074/jbc.C200378200 | doi-access = free }}</ref> 
* [[TOP2B]],<ref name = pmid11062478>{{cite journal | vauthors = Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E | title = Histone deacetylase interacts directly with DNA topoisomerase II | journal = Nature Genetics | volume = 26 | issue = 3 | pages = 349–353 | date = November 2000 | pmid = 11062478 | doi = 10.1038/81671 | s2cid = 19301396 }}</ref>  and
* [[YY1]].<ref name = pmid9346952>{{cite journal | vauthors = Yang WM, Yao YL, Sun JM, Davie JR, Seto E | title = Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family | journal = The Journal of Biological Chemistry | volume = 272 | issue = 44 | pages = 28001–28007 | date = October 1997 | pmid = 9346952 | doi = 10.1074/jbc.272.44.28001 | doi-access = free }}</ref><ref name = pmid11486036>{{cite journal | vauthors = Yao YL, Yang WM, Seto E | title = Regulation of transcription factor YY1 by acetylation and deacetylation | journal = Molecular and Cellular Biology | volume = 21 | issue = 17 | pages = 5979–5991 | date = September 2001 | pmid = 11486036 | pmc = 87316 | doi = 10.1128/mcb.21.17.5979-5991.2001 }}</ref><ref name = pmid9016636>{{cite journal | vauthors = Kalenik JL, Chen D, Bradley ME, Chen SJ, Lee TC | title = Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1 | journal = Nucleic Acids Research | volume = 25 | issue = 4 | pages = 843–849 | date = February 1997 | pmid = 9016636 | pmc = 146511 | doi = 10.1093/nar/25.4.843 }}</ref> 
{{Div col end}}

== See also ==
* [[Histone deacetylase]]

== References ==
{{reflist|35em}}

== Further reading ==
{{refbegin|35em}}
* {{cite journal | vauthors = Ahringer J | title = NuRD and SIN3 histone deacetylase complexes in development | journal = Trends in Genetics | volume = 16 | issue = 8 | pages = 351–356 | date = August 2000 | pmid = 10904264 | doi = 10.1016/S0168-9525(00)02066-7 }}
* {{cite journal | vauthors = Verdin E, Dequiedt F, Kasler HG | title = Class II histone deacetylases: versatile regulators | journal = Trends in Genetics | volume = 19 | issue = 5 | pages = 286–293 | date = May 2003 | pmid = 12711221 | doi = 10.1016/S0168-9525(03)00073-8 | hdl = 2268/80861 | hdl-access = free }}
* {{cite journal | vauthors = Zhang Y, Dufau ML | title = Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 85 | issue = 2–5 | pages = 401–414 | date = June 2003 | pmid = 12943729 | doi = 10.1016/S0960-0760(03)00230-9 | s2cid = 28512341 | url = https://zenodo.org/record/1260176 }}
* {{cite journal | vauthors = Furukawa Y, Kawakami T, Sudo K, Inazawa J, Matsumine A, Akiyama T, Nakamura Y | title = Isolation and mapping of a human gene (RPD3L1) that is homologous to RPD3, a transcription factor in Saccharomyces cerevisiae | journal = Cytogenetics and Cell Genetics | volume = 73 | issue = 1–2 | pages = 130–133 | year = 1996 | pmid = 8646880 | doi = 10.1159/000134323 }}
* {{cite journal | vauthors = Yang WM, Inouye C, Zeng Y, Bearss D, Seto E | title = Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 23 | pages = 12845–12850 | date = November 1996 | pmid = 8917507 | pmc = 24008 | doi = 10.1073/pnas.93.23.12845 | doi-access = free | bibcode = 1996PNAS...9312845Y }}
* {{cite journal | vauthors = Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN | title = Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression | journal = Cell | volume = 89 | issue = 3 | pages = 349–356 | date = May 1997 | pmid = 9150134 | doi = 10.1016/S0092-8674(00)80215-9 | s2cid = 13490886 | doi-access = free }}
* {{cite journal | vauthors = Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D | title = Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex | journal = Cell | volume = 89 | issue = 3 | pages = 357–364 | date = May 1997 | pmid = 9150135 | doi = 10.1016/S0092-8674(00)80216-0 | doi-access = free }}
* {{cite journal | vauthors = Yang WM, Yao YL, Sun JM, Davie JR, Seto E | title = Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family | journal = The Journal of Biological Chemistry | volume = 272 | issue = 44 | pages = 28001–28007 | date = October 1997 | pmid = 9346952 | doi = 10.1074/jbc.272.44.28001 | doi-access = free }}
* {{cite journal | vauthors = Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL | title = A role for histone deacetylase activity in HDAC1-mediated transcriptional repression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 7 | pages = 3519–3524 | date = March 1998 | pmid = 9520398 | pmc = 19868 | doi = 10.1073/pnas.95.7.3519 | doi-access = free | bibcode = 1998PNAS...95.3519H }}
* {{cite journal | vauthors = Randhawa GS, Bell DW, Testa JR, Feinberg AP | title = Identification and mapping of human histone acetylation modifier gene homologues | journal = Genomics | volume = 51 | issue = 2 | pages = 262–269 | date = July 1998 | pmid = 9722949 | doi = 10.1006/geno.1998.5370 | doi-access = free }}
* {{cite journal | vauthors = Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D | title = The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities | journal = Cell | volume = 95 | issue = 2 | pages = 279–289 | date = October 1998 | pmid = 9790534 | doi = 10.1016/S0092-8674(00)81758-4 | s2cid = 18786866 | doi-access = free }}
* {{cite journal | vauthors = Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL | title = Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex | journal = Nature | volume = 395 | issue = 6705 | pages = 917–921 | date = October 1998 | pmid = 9804427 | doi = 10.1038/27699 | s2cid = 4355885 | bibcode = 1998Natur.395..917T }}
* {{cite journal | vauthors = Hsieh JJ, Zhou S, Chen L, Young DB, Hayward SD | title = CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 1 | pages = 23–28 | date = January 1999 | pmid = 9874765 | pmc = 15086 | doi = 10.1073/pnas.96.1.23 | doi-access = free | bibcode = 1999PNAS...96...23H }}
* {{cite journal | vauthors = Yarden RI, Brody LC | title = BRCA1 interacts with components of the histone deacetylase complex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 9 | pages = 4983–4988 | date = April 1999 | pmid = 10220405 | pmc = 21803 | doi = 10.1073/pnas.96.9.4983 | doi-access = free | bibcode = 1999PNAS...96.4983Y }}
* {{cite journal | vauthors = Koipally J, Renold A, Kim J, Georgopoulos K | title = Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes | journal = The EMBO Journal | volume = 18 | issue = 11 | pages = 3090–3100 | date = June 1999 | pmid = 10357820 | pmc = 1171390 | doi = 10.1093/emboj/18.11.3090 }}
* {{cite journal | vauthors = Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D | title = Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation | journal = Genes & Development | volume = 13 | issue = 15 | pages = 1924–1935 | date = August 1999 | pmid = 10444591 | pmc = 316920 | doi = 10.1101/gad.13.15.1924 }}
* {{cite journal | vauthors = Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A | display-authors = 6 | title = MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex | journal = Nature Genetics | volume = 23 | issue = 1 | pages = 58–61 | date = September 1999 | pmid = 10471499 | doi = 10.1038/12659 | hdl-access = free | s2cid = 6147725 | hdl = 1842/684 }}
* {{cite journal | vauthors = Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP | title = Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation | journal = Nature Genetics | volume = 23 | issue = 1 | pages = 62–66 | date = September 1999 | pmid = 10471500 | doi = 10.1038/12664 | s2cid = 52868103 }}
* {{cite journal | vauthors = Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE | title = RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins | journal = Molecular and Cellular Biology | volume = 19 | issue = 10 | pages = 6632–6641 | date = October 1999 | pmid = 10490602 | pmc = 84642 | doi = 10.1128/mcb.19.10.6632 }}
{{refend}}

== External links ==
* {{MeshName|HDAC2+protein,+human}}
* {{FactorBook|HDAC2}}
* {{PDBe-KB2|Q92769|Histone deacetylase 2}}

{{Carbon-nitrogen non-peptide hydrolases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:EC 3.5.1]]