From Wikipedia, the free encyclopedia
HDAC4
Available structures
PDB Ortholog search:
PDBe
RCSB List of PDB id codes
2H8N ,
2O94 ,
2VQJ ,
2VQM ,
2VQO ,
2VQQ ,
2VQV ,
2VQW ,
3UXG ,
3UZD ,
3V31 ,
4CBT ,
4CBY ,
5A2S
Identifiers
Aliases
HDAC4 , AHO3, BDMR, HA6116, HD4, HDAC-4, HDAC-A, HDACA, histone deacetylase 4, NEDCHIDExternal IDs
OMIM :
605314
MGI :
3036234
HomoloGene :
55946
GeneCards :
HDAC4
Wikidata
Histone deacetylase 4 , also known as HDAC4 , is a
protein that in humans is encoded by the HDAC4
gene .
[5]
[6]
Function
Histones play a critical role in
transcriptional regulation ,
cell cycle progression, and developmental events. Histone
acetylation /deacetylation alters
chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the
histone deacetylase /acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly but through
transcription factors
MEF2C and
MEF2D . It seems to interact in a multiprotein complex with RbAp48 and HDAC3.
[7] Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.
[8]
Clinical significance
Studies have shown that HDAC4 regulates bone and muscle development.
Harvard University researchers also concluded that it promotes healthy vision: Reduced levels of the protein led to the death of the rod
photoreceptors and bipolar cells in the
retinas of mice.
[9]
[10]
Interactions
HDAC4 has been shown to
interact with:
BCL6 ,
[11]
BTG2 ,
[12]
[13]
CBX5 ,
[14]
GATA1 ,
[15]
HDAC3 ,
[5]
[16]
[17]
[18]
MAPK1 ,
[19]
MAPK3 ,
[19]
MEF2C ,
[20]
[21]
Myocyte-specific enhancer factor 2A ,
[22]
[23]
Nuclear receptor co-repressor 1 ,
[16]
[24]
Nuclear receptor co-repressor 2 ,
[16]
[24]
Testicular receptor 2 ,
[25]
[26]
YWHAB ,
[17]
YWHAE ,
[17]
[27] and
Zinc finger and BTB domain-containing protein 16 .
[11]
[28]
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000068024 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000026313 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
a
b Grozinger CM, Hassig CA, Schreiber SL (April 1999).
"Three proteins define a class of human histone deacetylases related to yeast Hda1p" . Proceedings of the National Academy of Sciences of the United States of America . 96 (9): 4868–73.
Bibcode :
1999PNAS...96.4868G .
doi :
10.1073/pnas.96.9.4868 .
PMC
21783 .
PMID
10220385 .
^ Fischle W, Emiliani S, Hendzel MJ, Nagase T, Nomura N, Voelter W, Verdin E (April 1999).
"A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p" . The Journal of Biological Chemistry . 274 (17): 11713–20.
doi :
10.1074/jbc.274.17.11713 .
PMID
10206986 .
^
"Entrez Gene: HDAC4 histone deacetylase 4" .
^ Glenisson W, Castronovo V, Waltregny D (October 2007).
"Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation" . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1773 (10): 1572–82.
doi :
10.1016/j.bbamcr.2007.05.016 .
PMID
17610967 .
^ Protein for Sight ,
Scientific American , 300 , 3 (March 2009), p. 23
^ Chen B, Cepko CL (January 2009).
"HDAC4 regulates neuronal survival in normal and diseased retinas" . Science . 323 (5911): 256–9.
doi :
10.1126/science.1166226 .
PMC
3339762 .
PMID
19131628 .
^
a
b Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S (June 2002).
"Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor" . The Journal of Biological Chemistry . 277 (24): 22045–52.
doi :
10.1074/jbc.M201736200 .
PMID
11929873 .
^ Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F (July 2007).
"Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3" . FASEB Journal . 21 (9): 2215–25.
doi :
10.1096/fj.06-7548com .
PMID
17371797 .
S2CID
4974360 .
^ Micheli L, D'Andrea G, Leonardi L, Tirone F (July 2017).
"HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression" (PDF) . Journal of Cellular Physiology . 232 (7): 1696–1707.
doi :
10.1002/jcp.25467 .
PMID
27333946 .
S2CID
4070837 .
^ Zhang CL, McKinsey TA, Olson EN (October 2002).
"Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation" . Molecular and Cellular Biology . 22 (20): 7302–12.
doi :
10.1128/mcb.22.20.7302-7312.2002 .
PMC
139799 .
PMID
12242305 .
^ Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H (December 2003).
"Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation" . Oncogene . 22 (57): 9176–84.
doi :
10.1038/sj.onc.1206902 .
PMID
14668799 .
^
a
b
c 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". Molecular Cell . 9 (1): 45–57.
doi :
10.1016/s1097-2765(01)00429-4 .
hdl :
11858/00-001M-0000-002C-9FF9-9 .
PMID
11804585 .
^
a
b
c Grozinger CM, Schreiber SL (July 2000).
"Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization" . Proceedings of the National Academy of Sciences of the United States of America . 97 (14): 7835–40.
Bibcode :
2000PNAS...97.7835G .
doi :
10.1073/pnas.140199597 .
PMC
16631 .
PMID
10869435 .
^ 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" . The Journal of Biological Chemistry . 276 (38): 35826–35.
doi :
10.1074/jbc.M104935200 .
PMID
11466315 .
^
a
b Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000).
"Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras" . Proceedings of the National Academy of Sciences of the United States of America . 97 (26): 14329–33.
Bibcode :
2000PNAS...9714329Z .
doi :
10.1073/pnas.250494697 .
PMC
18918 .
PMID
11114188 .
^ Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (November 1999).
"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor" . Molecular and Cellular Biology . 19 (11): 7816–27.
doi :
10.1128/mcb.19.11.7816 .
PMC
84849 .
PMID
10523670 .
^ Wang AH, Yang XJ (September 2001).
"Histone deacetylase 4 possesses intrinsic nuclear import and export signals" . Molecular and Cellular Biology . 21 (17): 5992–6005.
doi :
10.1128/mcb.21.17.5992-6005.2001 .
PMC
87317 .
PMID
11486037 .
^ Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T (September 1999).
"HDAC4 deacetylase associates with and represses the MEF2 transcription factor" . The EMBO Journal . 18 (18): 5099–107.
doi :
10.1093/emboj/18.18.5099 .
PMC
1171580 .
PMID
10487761 .
^ Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S (May 2000).
"mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity" (PDF) . The Journal of Biological Chemistry . 275 (20): 15594–9.
doi :
10.1074/jbc.M908437199 .
PMID
10748098 .
S2CID
39220205 .
^
a
b Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA (January 2000).
"Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway" . Genes & Development . 14 (1): 45–54.
doi :
10.1101/gad.14.1.45 .
PMC
316335 .
PMID
10640275 .
^ Franco PJ, Li G, Wei LN (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Molecular and Cellular Endocrinology . 206 (1–2): 1–12.
doi :
10.1016/s0303-7207(03)00254-5 .
PMID
12943985 .
S2CID
19487189 .
^ Franco PJ, Farooqui M, Seto E, Wei LN (August 2001).
"The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases" . Molecular Endocrinology . 15 (8): 1318–28.
doi :
10.1210/mend.15.8.0682 .
PMID
11463856 .
^ Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T (August 2001).
"Differential localization of HDAC4 orchestrates muscle differentiation" . Nucleic Acids Research . 29 (16): 3439–47.
doi :
10.1093/nar/29.16.3439 .
PMC
55849 .
PMID
11504882 .
^ Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A (November 2004).
"HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF" . Oncogene . 23 (54): 8777–84.
doi :
10.1038/sj.onc.1208128 .
PMID
15467736 .
Further reading
Pazin MJ, Kadonaga JT (May 1997).
"What's up and down with histone deacetylation and transcription?" . Cell . 89 (3): 325–8.
doi :
10.1016/S0092-8674(00)80211-1 .
PMID
9150131 .
S2CID
11488594 .
Verdin E, Dequiedt F, Kasler HG (May 2003). "Class II histone deacetylases: versatile regulators". Trends in Genetics . 19 (5): 286–93.
doi :
10.1016/S0168-9525(03)00073-8 .
hdl :
2268/80861 .
PMID
12711221 .
Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry . 236 (1): 107–13.
doi :
10.1006/abio.1996.0138 .
PMID
8619474 .
Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997).
"Large-scale concatenation cDNA sequencing" . Genome Research . 7 (4): 353–8.
doi :
10.1101/gr.7.4.353 .
PMC
139146 .
PMID
9110174 .
Wolffe AP (May 1997).
"Transcriptional control. Sinful repression" . Nature . 387 (6628): 16–7.
doi :
10.1038/387016a0 .
PMID
9139815 .
S2CID
29803420 .
Ohara O, Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Nomura N (February 1997).
"Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins" . DNA Research . 4 (1): 53–9.
doi :
10.1093/dnares/4.1.53 .
PMID
9179496 .
Fischle W, Emiliani S, Hendzel MJ, Nagase T, Nomura N, Voelter W, Verdin E (April 1999).
"A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p" . The Journal of Biological Chemistry . 274 (17): 11713–20.
doi :
10.1074/jbc.274.17.11713 .
PMID
10206986 .
Grozinger CM, Hassig CA, Schreiber SL (April 1999).
"Three proteins define a class of human histone deacetylases related to yeast Hda1p" . Proceedings of the National Academy of Sciences of the United States of America . 96 (9): 4868–73.
Bibcode :
1999PNAS...96.4868G .
doi :
10.1073/pnas.96.9.4868 .
PMC
21783 .
PMID
10220385 .
Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T (September 1999).
"HDAC4 deacetylase associates with and represses the MEF2 transcription factor" . The EMBO Journal . 18 (18): 5099–107.
doi :
10.1093/emboj/18.18.5099 .
PMC
1171580 .
PMID
10487761 .
Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (November 1999).
"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor" . Molecular and Cellular Biology . 19 (11): 7816–27.
doi :
10.1128/mcb.19.11.7816 .
PMC
84849 .
PMID
10523670 .
Youn HD, Grozinger CM, Liu JO (July 2000).
"Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4" . The Journal of Biological Chemistry . 275 (29): 22563–7.
doi :
10.1074/jbc.C000304200 .
PMID
10825153 .
Grozinger CM, Schreiber SL (July 2000).
"Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization" . Proceedings of the National Academy of Sciences of the United States of America . 97 (14): 7835–40.
Bibcode :
2000PNAS...97.7835G .
doi :
10.1073/pnas.140199597 .
PMC
16631 .
PMID
10869435 .
Huynh KD, Fischle W, Verdin E, Bardwell VJ (July 2000).
"BCoR, a novel corepressor involved in BCL-6 repression" . Genes & Development . 14 (14): 1810–23.
doi :
10.1101/gad.14.14.1810 .
PMC
316791 .
PMID
10898795 .
Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J (August 2000).
"Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3" . The EMBO Journal . 19 (16): 4342–50.
doi :
10.1093/emboj/19.16.4342 .
PMC
302030 .
PMID
10944117 .
Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP, Yang XJ (September 2000).
"Regulation of histone deacetylase 4 by binding of 14-3-3 proteins" . Molecular and Cellular Biology . 20 (18): 6904–12.
doi :
10.1128/MCB.20.18.6904-6912.2000 .
PMC
88766 .
PMID
10958686 .
Zhang CL, McKinsey TA, Lu JR, Olson EN (January 2001).
"Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor" . The Journal of Biological Chemistry . 276 (1): 35–9.
doi :
10.1074/jbc.M007364200 .
PMID
11022042 .
McKinsey TA, Zhang CL, Lu J, Olson EN (November 2000).
"Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation" . Nature . 408 (6808): 106–11.
Bibcode :
2000Natur.408..106M .
doi :
10.1038/35040593 .
PMC
4459600 .
PMID
11081517 .
Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000).
"Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras" . Proceedings of the National Academy of Sciences of the United States of America . 97 (26): 14329–33.
Bibcode :
2000PNAS...9714329Z .
doi :
10.1073/pnas.250494697 .
PMC
18918 .
PMID
11114188 .
McKinsey TA, Zhang CL, Olson EN (December 2000).
"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5" . Proceedings of the National Academy of Sciences of the United States of America . 97 (26): 14400–5.
Bibcode :
2000PNAS...9714400M .
doi :
10.1073/pnas.260501497 .
PMC
18930 .
PMID
11114197 .
External links
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .
Activity Regulation Classification Kinetics Types