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{{Infobox_gene}}
{{Infobox_gene}}
'''Histone deacetylase 2''' ('''HDAC2''') is an [[enzyme]] that in humans is encoded by the ''HDAC2'' [[gene]].<ref name="pmid9782097">{{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 = 245–6 | date = December 1998 | pmid = 9782097 | pmc = | doi = 10.1006/geno.1998.5435 }}</ref>
'''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|date=December 1998|title=Human histone deacetylase 2, HDAC2 (Human RPD3), is localized to 6q21 by radiation hybrid mapping|journal=Genomics|volume=52|issue=2|pages=245–6|doi=10.1006/geno.1998.5435|pmc=|pmid=9782097}}</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|histones]] (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 other 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|last=Seto|first=Edward|last2=Yoshida|first2=Minoru|date=2014-4|title=Erasers of Histone Acetylation: The Histone Deacetylase Enzymes|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970420/|journal=Cold Spring Harbor Perspectives in Biology|volume=6|issue=4|doi=10.1101/cshperspect.a018713|issn=1943-0264|pmc=PMCPMC3970420|pmid=24691964}}</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|last=Eom|first=Gwang Hyeon|last2=Nam|first2=Yoon Seok|last3=Oh|first3=Jae Gyun|last4=Choe|first4=Nakwon|last5=Min|first5=Hyun-Ki|last6=Yoo|first6=Eun-Kyung|last7=Kang|first7=Gaeun|last8=Nguyen|first8=Vu Hong|last9=Min|first9=Jung-Joon|date=2014-03-28|title=Regulation of acetylation of histone deacetylase 2 by p300/CBP-associated factor/histone deacetylase 5 in the development of cardiac hypertrophy|url=https://www.ncbi.nlm.nih.gov/pubmed/24526703|journal=Circulation Research|volume=114|issue=7|pages=1133–1143|doi=10.1161/CIRCRESAHA.114.303429|issn=1524-4571|pmid=24526703}}</ref>.

Generally, HDAC2 is considered a putative target for the treatment for a variety of diseases, due to its involvement in key cell cycle progressions. Specifically, HDAC2 has been shown to play a role in cardiac [[hypertrophy]]<ref name=":0" />, [[Alzheimer's disease]]<ref name=":1">{{Cite journal|last=Choubey|first=Sanjay K.|last2=Jeyakanthan|first2=Jeyaraman|date=2018-6|title=Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor - a novel target to prevent Alzheimer's disease|url=https://www.ncbi.nlm.nih.gov/pubmed/29932788/|journal=Journal of Receptor and Signal Transduction Research|volume=38|issue=3|pages=266–278|doi=10.1080/10799893.2018.1476541|issn=1532-4281|pmid=29932788}}</ref>, [[Parkinson's disease|Parkinson's Diseas]]<nowiki/>e <ref name=":2">{{Cite journal|last=Tan|first=Yuyan|last2=Delvaux|first2=Elaine|last3=Nolz|first3=Jennifer|last4=Coleman|first4=Paul D.|last5=Chen|first5=Shengdi|last6=Mastroeni|first6=Diego|date=08 2018|title=Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease|url=https://www.ncbi.nlm.nih.gov/pubmed/29803514/|journal=Neurobiology of Aging|volume=68|pages=134–141|doi=10.1016/j.neurobiolaging.2018.02.018|issn=1558-1497|pmid=29803514}}</ref>, [[acute myeloid leukemia]] (AML)<ref>{{Cite journal|last=Lei|first=Lijun|last2=Xia|first2=Siyu|last3=Liu|first3=Dan|last4=Li|first4=Xiaoqing|last5=Feng|first5=Jing|last6=Zhu|first6=Yaqi|last7=Hu|first7=Jun|last8=Xia|first8=Linjian|last9=Guo|first9=Lieping|date=07 20, 2018|title=Genome-wide characterization of lncRNAs in acute myeloid leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/28203711|journal=Briefings in Bioinformatics|volume=19|issue=4|pages=627–635|doi=10.1093/bib/bbx007|issn=1477-4054|pmc=PMCPMC6355113|pmid=28203711}}</ref>, [[osteosarcoma]]<ref>{{Cite journal|last=La Noce|first=Marcella|last2=Paino|first2=Francesca|last3=Mele|first3=Luigi|last4=Papaccio|first4=Gianpaolo|last5=Regad|first5=Tarik|last6=Lombardi|first6=Angela|last7=Papaccio|first7=Federica|last8=Desiderio|first8=Vincenzo|last9=Tirino|first9=Virginia|date=2018-12-03|title=HDAC2 depletion promotes osteosarcoma's stemness both in vitro and in vivo: a study on a putative new target for CSCs directed therapy|url=https://www.ncbi.nlm.nih.gov/pubmed/30509303/|journal=Journal of experimental & clinical cancer research: CR|volume=37|issue=1|pages=296|doi=10.1186/s13046-018-0978-x|issn=1756-9966|pmc=PMCPMC6276256|pmid=30509303}}</ref>, and [[Stomach cancer|Gastric Cancer]]<ref>{{Cite journal|last=Wei|first=Jun|last2=Wang|first2=Zijian|last3=Wang|first3=Zhixiang|last4=Yang|first4=Yong|last5=Fu|first5=Changlai|last6=Zhu|first6=Jianqing|last7=Jiang|first7=Danbin|date=2017|title=MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer|url=https://www.ncbi.nlm.nih.gov/pubmed/29333444|journal=BioMed Research International|volume=2017|pages=5348490|doi=10.1155/2017/5348490|issn=2314-6141|pmc=PMCPMC5733238|pmid=29333444}}</ref>.



== Structure and Mechanism ==
[[File:HDAC2_attacking_lysine_residue.pdf|link=https://en.wikipedia.org/wiki/File:HDAC2_attacking_lysine_residue.pdf|alt=|left|thumb|418x418px|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 either a Zn<sup>2+</sup> metal 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|last=Lombardi|first=Patrick M.|last2=Cole|first2=Kathryn E.|last3=Dowling|first3=Daniel P.|last4=Christianson|first4=David W.|date=2011-12|title=Structure, Mechanism, and Inhibition of Histone Deacetylases and Related Metalloenzymes|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232309/|journal=Current opinion in structural biology|volume=21|issue=6|pages=735–743|doi=10.1016/j.sbi.2011.08.004|issn=0959-440X|pmc=PMCPMC3232309|pmid=21872466}}</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>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S0960894X10004324?via%3Dihub|title=ScienceDirect|website=www.sciencedirect.com|doi=10.1016/j.bmcl.2010.03.091|access-date=2019-03-15}}</ref>







== Function ==
== Function ==
[[File:HDAC2_Chem_183.pdf|link=https://en.wikipedia.org/wiki/File:HDAC2_Chem_183.pdf|alt=|thumb|425x425px|The HDAC2 enzyme attacking a lysine residue.]]
⚫
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|accessdate=}}</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|last=Trivedi|first=Chinmay M.|last2=Luo|first2=Yang|last3=Yin|first3=Zhan|last4=Zhang|first4=Maozhen|last5=Zhu|first5=Wenting|last6=Wang|first6=Tao|last7=Floss|first7=Thomas|last8=Goettlicher|first8=Martin|last9=Noppinger|first9=Patricia Ruiz|date=2007-3|title=Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity|url=https://www.ncbi.nlm.nih.gov/pubmed/17322895|journal=Nature Medicine|volume=13|issue=3|pages=324–331|doi=10.1038/nm1552|issn=1078-8956|pmid=17322895}}</ref>.

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>{{Cite web|url=https://www.sciencedirect.com/science/article/pii/S096999611100249X?via%3Dihub|title=ScienceDirect|website=www.sciencedirect.com|doi=10.1016/j.nbd.2011.07.013|pmc=PMC3220746|pmid=21821124|access-date=2019-03-15}}</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|last=Alvarez|first=Alejandra R.|last2=Seto|first2=Edward|last3=Zanlungo|first3=Silvana|last4=Villagra|first4=Alejandro|last5=Chamorro|first5=David|last6=Estrada|first6=Lisbell D.|last7=Contreras|first7=Pablo S.|last8=Gonzalez-Zuñiga|first8=Marcelo|date=2014-10-02|title=c-Abl Stabilizes HDAC2 Levels by Tyrosine Phosphorylation Repressing Neuronal Gene Expression in Alzheimer’s Disease|url=https://www.cell.com/molecular-cell/abstract/S1097-2765(14)00646-7|journal=Molecular Cell|language=English|volume=56|issue=1|pages=163–173|doi=10.1016/j.molcel.2014.08.013|issn=1097-2765|pmid=25219501}}</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 protein in the substantia Nigra of the brain. In vivo evidence has shown a correlation between the number of microglial proteins and the upregulation of HDAC2<ref name=":2" />. It is thought therefore that HDAC2 inhibitors could be effective in treating microglial-initiated dopaminergic loss of neurons in the brain.


=== Cancer Therapy ===
⚫
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="entrez">{{cite web | title = Entrez Gene: HDAC2 histone deacetylase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3066| accessdate = }}</ref>
The role of HDAC2 in various forms of cancer such as osteosarcoma, gastric cancer, and acute myeloid leukemia have been studied. Current research is focused on creating inhibitors that decrease the upregulation of HDAC2.


== Interactions ==
== Interactions ==

Revision as of 05:56, 15 March 2019

HDAC2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHDAC2, HD2, RPD3, YAF1, histone deacetylase 2, KDAC2
External IDsOMIM: 605164 MGI: 1097691 HomoloGene: 68187 GeneCards: HDAC2
Orthologs
SpeciesHumanMouse
Entrez

3066

15182

Ensembl

ENSG00000196591

ENSMUSG00000019777

UniProt

Q92769

P70288

RefSeq (mRNA)

NM_001527

NM_008229

RefSeq (protein)

NP_001518

NP_032255

Location (UCSC)Chr 6: 113.93 – 114.01 MbChr 10: 36.85 – 36.88 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene.[5] 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 histones (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[6].

Though the functional role of the class to which HDAC2 belongs has been carefully studied, the mechanism by which HDAC2 interacts with other Histone deacetylases of other classes has yet to be elucidated. HDAC2 is broadly regulated by protein kinase 2 (CK2) and 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)[7]. 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[8].

Generally, HDAC2 is considered a putative target for the treatment for a variety of diseases, due to its involvement in key cell cycle progressions. Specifically, HDAC2 has been shown to play a role in cardiac hypertrophy[8], Alzheimer's disease[9], Parkinson's Disease [10], acute myeloid leukemia (AML)[11], osteosarcoma[12], and Gastric Cancer[13].


Structure and Mechanism

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 either a Zn2+ metal 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[14].

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[15]




Function

The HDAC2 enzyme attacking a lysine residue.

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.[16]

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[17].

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[8].

Alzheimer's Disease

It has been found that patients with Alzheimer's Disease experience a decrease in the expression of neuronal genes[18]. Furthermore, a recent study found that inhibition of HDAC2 via c-Abl by tyrosine phosphorylation prevented cognitive and behavioral impairments in mice with Alzheimer's Disease[19]. 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[9].

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 protein in the substantia Nigra of the brain. In vivo evidence has shown a correlation between the number of microglial proteins and the upregulation of HDAC2[10]. It is thought therefore that HDAC2 inhibitors could be effective in treating microglial-initiated dopaminergic loss of 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. Current research is focused on creating inhibitors that decrease the upregulation of HDAC2.

Interactions

Histone deacetylase 2 has been shown to interact with:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196591 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019777 – 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. ^ Betz R, Gray SG, Ekström C, Larsson C, Ekström TJ (December 1998). "Human histone deacetylase 2, HDAC2 (Human RPD3), is localized to 6q21 by radiation hybrid mapping". Genomics. 52 (2): 245–6. doi:10.1006/geno.1998.5435. PMID 9782097.
  6. ^ "Tissue expression of HDAC2 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2019-03-14.
  7. ^ Seto, Edward; Yoshida, Minoru (2014-4). "Erasers of Histone Acetylation: The Histone Deacetylase Enzymes". Cold Spring Harbor Perspectives in Biology. 6 (4). doi:10.1101/cshperspect.a018713. ISSN 1943-0264. PMC PMCPMC3970420. PMID 24691964. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  8. ^ a b c Eom, Gwang Hyeon; Nam, Yoon Seok; Oh, Jae Gyun; Choe, Nakwon; Min, Hyun-Ki; Yoo, Eun-Kyung; Kang, Gaeun; Nguyen, Vu Hong; Min, Jung-Joon (2014-03-28). "Regulation of acetylation of histone deacetylase 2 by p300/CBP-associated factor/histone deacetylase 5 in the development of cardiac hypertrophy". Circulation Research. 114 (7): 1133–1143. doi:10.1161/CIRCRESAHA.114.303429. ISSN 1524-4571. PMID 24526703.
  9. ^ a b Choubey, Sanjay K.; Jeyakanthan, Jeyaraman (2018-6). "Molecular dynamics and quantum chemistry-based approaches to identify isoform selective HDAC2 inhibitor - a novel target to prevent Alzheimer's disease". Journal of Receptor and Signal Transduction Research. 38 (3): 266–278. doi:10.1080/10799893.2018.1476541. ISSN 1532-4281. PMID 29932788. {{cite journal}}: Check date values in: |date= (help)
  10. ^ a b Tan, Yuyan; Delvaux, Elaine; Nolz, Jennifer; Coleman, Paul D.; Chen, Shengdi; Mastroeni, Diego (08 2018). "Upregulation of histone deacetylase 2 in laser capture nigral microglia in Parkinson's disease". Neurobiology of Aging. 68: 134–141. doi:10.1016/j.neurobiolaging.2018.02.018. ISSN 1558-1497. PMID 29803514. {{cite journal}}: Check date values in: |date= (help)
  11. ^ Lei, Lijun; Xia, Siyu; Liu, Dan; Li, Xiaoqing; Feng, Jing; Zhu, Yaqi; Hu, Jun; Xia, Linjian; Guo, Lieping (07 20, 2018). "Genome-wide characterization of lncRNAs in acute myeloid leukemia". Briefings in Bioinformatics. 19 (4): 627–635. doi:10.1093/bib/bbx007. ISSN 1477-4054. PMC PMCPMC6355113. PMID 28203711. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  12. ^ La Noce, Marcella; Paino, Francesca; Mele, Luigi; Papaccio, Gianpaolo; Regad, Tarik; Lombardi, Angela; Papaccio, Federica; Desiderio, Vincenzo; Tirino, Virginia (2018-12-03). "HDAC2 depletion promotes osteosarcoma's stemness both in vitro and in vivo: a study on a putative new target for CSCs directed therapy". Journal of experimental & clinical cancer research: CR. 37 (1): 296. doi:10.1186/s13046-018-0978-x. ISSN 1756-9966. PMC PMCPMC6276256. PMID 30509303. {{cite journal}}: Check |pmc= value (help)CS1 maint: unflagged free DOI (link)
  13. ^ Wei, Jun; Wang, Zijian; Wang, Zhixiang; Yang, Yong; Fu, Changlai; Zhu, Jianqing; Jiang, Danbin (2017). "MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer". BioMed Research International. 2017: 5348490. doi:10.1155/2017/5348490. ISSN 2314-6141. PMC PMCPMC5733238. PMID 29333444. {{cite journal}}: Check |pmc= value (help)CS1 maint: unflagged free DOI (link)
  14. ^ Lombardi, Patrick M.; Cole, Kathryn E.; Dowling, Daniel P.; Christianson, David W. (2011-12). "Structure, Mechanism, and Inhibition of Histone Deacetylases and Related Metalloenzymes". Current opinion in structural biology. 21 (6): 735–743. doi:10.1016/j.sbi.2011.08.004. ISSN 0959-440X. PMC PMCPMC3232309. PMID 21872466. {{cite journal}}: Check |pmc= value (help); Check date values in: |date= (help)
  15. ^ "ScienceDirect". www.sciencedirect.com. doi:10.1016/j.bmcl.2010.03.091. Retrieved 2019-03-15.
  16. ^ "Entrez Gene: HDAC2 histone deacetylase 2".
  17. ^ Trivedi, Chinmay M.; Luo, Yang; Yin, Zhan; Zhang, Maozhen; Zhu, Wenting; Wang, Tao; Floss, Thomas; Goettlicher, Martin; Noppinger, Patricia Ruiz (2007-3). "Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity". Nature Medicine. 13 (3): 324–331. doi:10.1038/nm1552. ISSN 1078-8956. PMID 17322895. {{cite journal}}: Check date values in: |date= (help)
  18. ^ "ScienceDirect". www.sciencedirect.com. doi:10.1016/j.nbd.2011.07.013. PMC 3220746. PMID 21821124. Retrieved 2019-03-15.{{cite web}}: CS1 maint: PMC format (link)
  19. ^ Alvarez, Alejandra R.; Seto, Edward; Zanlungo, Silvana; Villagra, Alejandro; Chamorro, David; Estrada, Lisbell D.; Contreras, Pablo S.; Gonzalez-Zuñiga, Marcelo (2014-10-02). "c-Abl Stabilizes HDAC2 Levels by Tyrosine Phosphorylation Repressing Neuronal Gene Expression in Alzheimer's Disease". Molecular Cell. 56 (1): 163–173. doi:10.1016/j.molcel.2014.08.013. ISSN 1097-2765. PMID 25219501.
  20. ^ a b Schmidt DR, Schreiber SL (November 1999). "Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4". Biochemistry. 38 (44): 14711–7. doi:10.1021/bi991614n. PMID 10545197.
  21. ^ a b c d Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang SG, Chun JS, Lee CW (September 2004). "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Lett. 575 (1–3): 23–9. doi:10.1016/j.febslet.2004.07.089. PMID 15388328.
  22. ^ a b c d e f g h i j Hakimi MA, Dong Y, Lane WS, Speicher DW, Shiekhattar R (February 2003). "A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes". J. Biol. Chem. 278 (9): 7234–9. doi:10.1074/jbc.M208992200. PMID 12493763.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  23. ^ a b c d e Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL (October 1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature. 395 (6705): 917–21. doi:10.1038/27699. PMID 9804427.
  24. ^ a b Hakimi MA, Bochar DA, Schmiesing JA, Dong Y, Barak OG, Speicher DW, Yokomori K, Shiekhattar R (August 2002). "A chromatin remodelling complex that loads cohesin onto human chromosomes". Nature. 418 (6901): 994–8. doi:10.1038/nature01024. PMID 12198550.
  25. ^ Rountree MR, Bachman KE, Baylin SB (July 2000). "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci". Nat. Genet. 25 (3): 269–77. doi:10.1038/77023. PMID 10888872.
  26. ^ a b c van der Vlag J, Otte AP (December 1999). "Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation". Nat. Genet. 23 (4): 474–8. doi:10.1038/70602. PMID 10581039.
  27. ^ Yang WM, Yao YL, Seto E. "The FK506-binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1". EMBO J. 20 (17): 4814–25. doi:10.1093/emboj/20.17.4814. PMC 125595. PMID 11532945.
  28. ^ "Three-way control of fetal heart-cell proliferation could help regenerate cardiac cells". October 7, 2010.
  29. ^ Wen YD, Cress WD, Roy AL, Seto E (January 2003). "Histone deacetylase 3 binds to and regulates the multifunctional transcription factor TFII-I". J. Biol. Chem. 278 (3): 1841–7. doi:10.1074/jbc.M206528200. PMID 12393887.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  30. ^ a b Fischer DD, Cai R, Bhatia U, Asselbergs FA, Song C, Terry R, Trogani N, Widmer R, Atadja P, Cohen D (February 2002). "Isolation and characterization of a novel class II histone deacetylase, HDAC10". J. Biol. Chem. 277 (8): 6656–66. doi:10.1074/jbc.M108055200. PMID 11739383.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  31. ^ a b c Yao YL, Yang WM (October 2003). "The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity". J. Biol. Chem. 278 (43): 42560–8. doi:10.1074/jbc.M302955200. PMID 12920132.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  32. ^ a b c d Hakimi MA, Bochar DA, Chenoweth J, Lane WS, Mandel G, Shiekhattar R. "A core-BRAF35 complex containing histone deacetylase mediates repression of neuronal-specific genes". Proc. Natl. Acad. Sci. U.S.A. 99 (11): 7420–5. doi:10.1073/pnas.112008599. PMC 124246. PMID 12032298.
  33. ^ a b Johnson CA, White DA, Lavender JS, O'Neill LP, Turner BM (March 2002). "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". J. Biol. Chem. 277 (11): 9590–7. doi:10.1074/jbc.M107942200. PMID 11777905.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  34. ^ Fischle W, Dequiedt F, Hendzel MJ, Guenther MG, Lazar MA, Voelter W, Verdin E (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Mol. Cell. 9 (1): 45–57. doi:10.1016/s1097-2765(01)00429-4. PMID 11804585.
  35. ^ Fischle W, Dequiedt F, Fillion M, Hendzel MJ, Voelter W, Verdin E (September 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". J. Biol. Chem. 276 (38): 35826–35. doi:10.1074/jbc.M104935200. PMID 11466315.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  36. ^ Ashburner BP, Westerheide SD, Baldwin AS. "The p65 (RelA) subunit of NF-kappaB interacts with the histone deacetylase (HDAC) corepressors HDAC1 and HDAC2 to negatively regulate gene expression". Mol. Cell. Biol. 21 (20): 7065–77. doi:10.1128/MCB.21.20.7065-7077.2001. PMC 99882. PMID 11564889.
  37. ^ a b c d Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D. "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 (15): 1924–35. doi:10.1101/gad.13.15.1924. PMC 316920. PMID 10444591.
  38. ^ Hassig CA, Tong JK, Fleischer TC, Owa T, Grable PG, Ayer DE, Schreiber SL. "A role for histone deacetylase activity in HDAC1-mediated transcriptional repression". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3519–24. doi:10.1073/pnas.95.7.3519. PMC 19868. PMID 9520398.
  39. ^ Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (May 1997). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell. 89 (3): 357–64. doi:10.1016/s0092-8674(00)80216-0. PMID 9150135.
  40. ^ Wysocka J, Myers MP, Laherty CD, Eisenman RN, Herr W. "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1". Genes Dev. 17 (7): 896–911. doi:10.1101/gad.252103. PMC 196026. PMID 12670868.
  41. ^ Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, Vadlamudi RK, Kumar R (January 2001). "Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor". Nat. Cell Biol. 3 (1): 30–7. doi:10.1038/35050532. PMID 11146623.
  42. ^ a b Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN (May 1997). "Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression". Cell. 89 (3): 349–56. doi:10.1016/s0092-8674(00)80215-9. PMID 9150134.
  43. ^ Spronk CA, Tessari M, Kaan AM, Jansen JF, Vermeulen M, Stunnenberg HG, Vuister GW (December 2000). "The Mad1-Sin3B interaction involves a novel helical fold". Nat. Struct. Biol. 7 (12): 1100–4. doi:10.1038/81944. PMID 11101889.
  44. ^ Brackertz M, Boeke J, Zhang R, Renkawitz R (October 2002). "Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3". J. Biol. Chem. 277 (43): 40958–66. doi:10.1074/jbc.M207467200. PMID 12183469.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  45. ^ Ng HH, Zhang Y, Hendrich B, Johnson CA, Turner BM, Erdjument-Bromage H, Tempst P, Reinberg D, Bird A (September 1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet. 23 (1): 58–61. doi:10.1038/12659. PMID 10471499.
  46. ^ Iwase S, Januma A, Miyamoto K, Shono N, Honda A, Yanagisawa J, Baba T (September 2004). "Characterization of BHC80 in BRAF-HDAC complex, involved in neuron-specific gene repression". Biochem. Biophys. Res. Commun. 322 (2): 601–8. doi:10.1016/j.bbrc.2004.07.163. PMID 15325272.
  47. ^ Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M (August 2003). "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". J. Biol. Chem. 278 (33): 30677–85. doi:10.1074/jbc.M302273200. PMID 12788942.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  48. ^ a b Zhang Y, Dufau ML (June 2003). "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". J. Steroid Biochem. Mol. Biol. 85 (2–5): 401–14. doi:10.1016/s0960-0760(03)00230-9. PMID 12943729.
  49. ^ a b c Zhang Y, Dufau ML (September 2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". J. Biol. Chem. 277 (36): 33431–8. doi:10.1074/jbc.M204417200. PMID 12091390.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  50. ^ You A, Tong JK, Grozinger CM, Schreiber SL. "CoREST is an integral component of the CoREST- human histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 98 (4): 1454–8. doi:10.1073/pnas.98.4.1454. PMC 29278. PMID 11171972.
  51. ^ Kiernan R, Brès V, Ng RW, Coudart MP, El Messaoudi S, Sardet C, Jin DY, Emiliani S, Benkirane M (January 2003). "Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65". J. Biol. Chem. 278 (4): 2758–66. doi:10.1074/jbc.M209572200. PMID 12419806.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  52. ^ Yu Z, Zhang W, Kone BC (August 2002). "Histone deacetylases augment cytokine induction of the iNOS gene". J. Am. Soc. Nephrol. 13 (8): 2009–17. doi:10.1097/01.asn.0000024253.59665.f1. PMID 12138131.
  53. ^ Lai A, Lee JM, Yang WM, DeCaprio JA, Kaelin WG, Seto E, Branton PE. "RBP1 recruits both histone deacetylase-dependent and -independent repression activities to retinoblastoma family proteins". Mol. Cell. Biol. 19 (10): 6632–41. doi:10.1128/mcb.19.10.6632. PMC 84642. PMID 10490602.
  54. ^ Zhang Y, Sun ZW, Iratni R, Erdjument-Bromage H, Tempst P, Hampsey M, Reinberg D (June 1998). "SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex". Mol. Cell. 1 (7): 1021–31. doi:10.1016/s1097-2765(00)80102-1. PMID 9651585.
  55. ^ Kuzmichev A, Zhang Y, Erdjument-Bromage H, Tempst P, Reinberg D. "Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)". Mol. Cell. Biol. 22 (3): 835–48. doi:10.1128/mcb.22.3.835-848.2002. PMC 133546. PMID 11784859.
  56. ^ Fleischer TC, Yun UJ, Ayer DE. "Identification and characterization of three new components of the mSin3A corepressor complex". Mol. Cell. Biol. 23 (10): 3456–67. doi:10.1128/mcb.23.10.3456-3467.2003. PMC 164750. PMID 12724404.
  57. ^ Yang L, Mei Q, Zielinska-Kwiatkowska A, Matsui Y, Blackburn ML, Benedetti D, Krumm AA, Taborsky GJ, Chansky HA. "An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B". Biochem. J. 369 (Pt 3): 651–7. doi:10.1042/BJ20020854. PMC 1223118. PMID 12398767.
  58. ^ Zhou S, Fujimuro M, Hsieh JJ, Chen L, Hayward SD. "A role for SKIP in EBNA2 activation of CBF1-repressed promoters". J. Virol. 74 (4): 1939–47. doi:10.1128/jvi.74.4.1939-1947.2000. PMC 111672. PMID 10644367.
  59. ^ Vaute O, Nicolas E, Vandel L, Trouche D. "Functional and physical interaction between the histone methyl transferase Suv39H1 and histone deacetylases". Nucleic Acids Res. 30 (2): 475–81. doi:10.1093/nar/30.2.475. PMC 99834. PMID 11788710.
  60. ^ a b Won J, Yim J, Kim TK (October 2002). "Sp1 and Sp3 recruit histone deacetylase to repress transcription of human telomerase reverse transcriptase (hTERT) promoter in normal human somatic cells". J. Biol. Chem. 277 (41): 38230–8. doi:10.1074/jbc.M206064200. PMID 12151407.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  61. ^ a b Sun JM, Chen HY, Moniwa M, Litchfield DW, Seto E, Davie JR (September 2002). "The transcriptional repressor Sp3 is associated with CK2-phosphorylated histone deacetylase 2". J. Biol. Chem. 277 (39): 35783–6. doi:10.1074/jbc.C200378200. PMID 12176973.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  62. ^ Tsai SC, Valkov N, Yang WM, Gump J, Sullivan D, Seto E (November 2000). "Histone deacetylase interacts directly with DNA topoisomerase II". Nat. Genet. 26 (3): 349–53. doi:10.1038/81671. PMID 11062478.
  63. ^ Yang WM, Yao YL, Sun JM, Davie JR, Seto E (October 1997). "Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family". J. Biol. Chem. 272 (44): 28001–7. doi:10.1074/jbc.272.44.28001. PMID 9346952.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  64. ^ Yao YL, Yang WM, Seto E. "Regulation of transcription factor YY1 by acetylation and deacetylation". Mol. Cell. Biol. 21 (17): 5979–91. doi:10.1128/mcb.21.17.5979-5991.2001. PMC 87316. PMID 11486036.
  65. ^ Kalenik JL, Chen D, Bradley ME, Chen SJ, Lee TC. "Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1". Nucleic Acids Res. 25 (4): 843–9. doi:10.1093/nar/25.4.843. PMC 146511. PMID 9016636.

Further reading

External links

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