HDAC4

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.{{cite web | title = Entrez Gene: HDAC4 histone deacetylase 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9759}} Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.{{cite journal | vauthors = Glenisson W, Castronovo V, Waltregny D | title = Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | volume = 1773 | issue = 10 | pages = 1572–82 | date = October 2007 | pmid = 17610967 | doi = 10.1016/j.bbamcr.2007.05.016 | doi-access = free }}

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.Protein for Sight, Scientific American, 300, 3 (March 2009), p. 23{{cite journal | vauthors = Chen B, Cepko CL | title = HDAC4 regulates neuronal survival in normal and diseased retinas | journal = Science | volume = 323 | issue = 5911 | pages = 256–9 | date = January 2009 | pmid = 19131628 | pmc = 3339762 | doi = 10.1126/science.1166226 }}

HDAC4 has been shown to interact with:

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• BCL6,
• BTG2,{{cite journal | vauthors = Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F | title = Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3 | journal = FASEB Journal | volume = 21 | issue = 9 | pages = 2215–25 | date = July 2007 | pmid = 17371797 | doi = 10.1096/fj.06-7548com | s2cid = 4974360 | doi-access = free }}{{cite journal | vauthors = Micheli L, D'Andrea G, Leonardi L, Tirone F | title = HDAC1, HDAC4, and HDAC9 Bind to PC3/Tis21/Btg2 and Are Required for Its Inhibition of Cell Cycle Progression and Cyclin D1 Expression | journal = Journal of Cellular Physiology | volume = 232 | issue = 7 | pages = 1696–1707 | date = July 2017 | pmid = 27333946 | doi = 10.1002/jcp.25467 | s2cid = 4070837 | url = http://www.inmm.cnr.it/tirone/pdfs/Micheli_et_al-2017-J_Cell_Physiol%20PC3-HDACs.pdf }}
• CBX5,{{cite journal | vauthors = Zhang CL, McKinsey TA, Olson EN | title = Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation | journal = Molecular and Cellular Biology | volume = 22 | issue = 20 | pages = 7302–12 | date = October 2002 | pmid = 12242305 | pmc = 139799 | doi = 10.1128/mcb.22.20.7302-7312.2002 }}
• GATA1,{{cite journal | vauthors = Watamoto K, Towatari M, Ozawa Y, Miyata Y, Okamoto M, Abe A, Naoe T, Saito H | title = Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation | journal = Oncogene | volume = 22 | issue = 57 | pages = 9176–84 | date = December 2003 | pmid = 14668799 | doi = 10.1038/sj.onc.1206902 | doi-access = free }}
• HDAC3,{{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 = 35826–35 | date = September 2001 | pmid = 11466315 | doi = 10.1074/jbc.M104935200 | doi-access = free }}
• MAPK1,
• MAPK3,{{cite journal | vauthors = Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA | title = Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 26 | pages = 14329–33 | date = December 2000 | pmid = 11114188 | pmc = 18918 | doi = 10.1073/pnas.250494697 | bibcode = 2000PNAS...9714329Z | doi-access = free }}
• MEF2C,{{cite journal | vauthors = Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ | title = HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor | journal = Molecular and Cellular Biology | volume = 19 | issue = 11 | pages = 7816–27 | date = November 1999 | pmid = 10523670 | pmc = 84849 | doi = 10.1128/mcb.19.11.7816 }}{{cite journal | vauthors = Wang AH, Yang XJ | title = Histone deacetylase 4 possesses intrinsic nuclear import and export signals | journal = Molecular and Cellular Biology | volume = 21 | issue = 17 | pages = 5992–6005 | date = September 2001 | pmid = 11486037 | pmc = 87317 | doi = 10.1128/mcb.21.17.5992-6005.2001 }}
• Myocyte-specific enhancer factor 2A,{{cite journal | vauthors = Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T | title = HDAC4 deacetylase associates with and represses the MEF2 transcription factor | journal = The EMBO Journal | volume = 18 | issue = 18 | pages = 5099–107 | date = September 1999 | pmid = 10487761 | pmc = 1171580 | doi = 10.1093/emboj/18.18.5099 }}{{cite journal | vauthors = Lemercier C, Verdel A, Galloo B, Curtet S, Brocard MP, Khochbin S | title = mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity | journal = The Journal of Biological Chemistry | volume = 275 | issue = 20 | pages = 15594–9 | date = May 2000 | pmid = 10748098 | doi = 10.1074/jbc.M908437199 | s2cid = 39220205 | url = https://hal.archives-ouvertes.fr/hal-00379796/file/Lemercier_JBC_2000.pdf | doi-access = free }}
• Nuclear receptor co-repressor 1,{{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 = 11858/00-001M-0000-002C-9FF9-9 | hdl-access = free }}{{cite journal | vauthors = Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA | title = Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway | journal = Genes & Development | volume = 14 | issue = 1 | pages = 45–54 | date = January 2000 | doi = 10.1101/gad.14.1.45 | pmid = 10640275 | pmc = 316335 }}
• Nuclear receptor co-repressor 2,
• Testicular receptor 2,{{cite journal | vauthors = Franco PJ, Li G, Wei LN | title = Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase | journal = Molecular and Cellular Endocrinology | volume = 206 | issue = 1–2 | pages = 1–12 | date = August 2003 | pmid = 12943985 | doi = 10.1016/s0303-7207(03)00254-5 | s2cid = 19487189 }}{{cite journal | vauthors = Franco PJ, Farooqui M, Seto E, Wei LN | title = The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases | journal = Molecular Endocrinology | volume = 15 | issue = 8 | pages = 1318–28 | date = August 2001 | pmid = 11463856 | doi = 10.1210/mend.15.8.0682 | doi-access = free }}
• YWHAB,{{cite journal | vauthors = Grozinger CM, Schreiber SL | title = Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 7835–40 | date = July 2000 | pmid = 10869435 | pmc = 16631 | doi = 10.1073/pnas.140199597 | bibcode = 2000PNAS...97.7835G | doi-access = free }}
• YWHAE,{{cite journal | vauthors = Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T | title = Differential localization of HDAC4 orchestrates muscle differentiation | journal = Nucleic Acids Research | volume = 29 | issue = 16 | pages = 3439–47 | date = August 2001 | pmid = 11504882 | pmc = 55849 | doi = 10.1093/nar/29.16.3439 }} and
• Zinc finger and BTB domain-containing protein 16.{{cite journal | vauthors = Lemercier C, Brocard MP, Puvion-Dutilleul F, Kao HY, Albagli O, Khochbin S | title = Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor | journal = The Journal of Biological Chemistry | volume = 277 | issue = 24 | pages = 22045–52 | date = June 2002 | pmid = 11929873 | doi = 10.1074/jbc.M201736200 | doi-access = free }}{{cite journal | vauthors = Chauchereau A, Mathieu M, de Saintignon J, Ferreira R, Pritchard LL, Mishal Z, Dejean A, Harel-Bellan A | title = HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF | journal = Oncogene | volume = 23 | issue = 54 | pages = 8777–84 | date = November 2004 | pmid = 15467736 | doi = 10.1038/sj.onc.1208128 | doi-access = free }}

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• Histone deacetylase

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• {{cite journal | vauthors = Pazin MJ, Kadonaga JT | title = What's up and down with histone deacetylation and transcription? | journal = Cell | volume = 89 | issue = 3 | pages = 325–8 | date = May 1997 | pmid = 9150131 | doi = 10.1016/S0092-8674(00)80211-1 | s2cid = 11488594 | doi-access = free }}
• {{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 = 286–93 | date = May 2003 | pmid = 12711221 | doi = 10.1016/S0168-9525(03)00073-8 | hdl = 2268/80861 | hdl-access = free }}
• {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
• {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
• {{cite journal | vauthors = Wolffe AP | title = Transcriptional control. Sinful repression | journal = Nature | volume = 387 | issue = 6628 | pages = 16–7 | date = May 1997 | pmid = 9139815 | doi = 10.1038/387016a0 | s2cid = 29803420 | url = https://zenodo.org/record/1233198 | doi-access = free }}
• {{cite journal | vauthors = Ohara O, Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Nomura N | title = Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins | journal = DNA Research | volume = 4 | issue = 1 | pages = 53–9 | date = February 1997 | pmid = 9179496 | doi = 10.1093/dnares/4.1.53 | doi-access = free }}
• {{cite journal | vauthors = Fischle W, Emiliani S, Hendzel MJ, Nagase T, Nomura N, Voelter W, Verdin E | title = A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p | journal = The Journal of Biological Chemistry | volume = 274 | issue = 17 | pages = 11713–20 | date = April 1999 | pmid = 10206986 | doi = 10.1074/jbc.274.17.11713 | doi-access = free }}
• {{cite journal | vauthors = Grozinger CM, Hassig CA, Schreiber SL | title = Three proteins define a class of human histone deacetylases related to yeast Hda1p | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 9 | pages = 4868–73 | date = April 1999 | pmid = 10220385 | pmc = 21783 | doi = 10.1073/pnas.96.9.4868 | bibcode = 1999PNAS...96.4868G | doi-access = free }}
• {{cite journal | vauthors = Miska EA, Karlsson C, Langley E, Nielsen SJ, Pines J, Kouzarides T | title = HDAC4 deacetylase associates with and represses the MEF2 transcription factor | journal = The EMBO Journal | volume = 18 | issue = 18 | pages = 5099–107 | date = September 1999 | pmid = 10487761 | pmc = 1171580 | doi = 10.1093/emboj/18.18.5099 }}
• {{cite journal | vauthors = Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ | title = HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor | journal = Molecular and Cellular Biology | volume = 19 | issue = 11 | pages = 7816–27 | date = November 1999 | pmid = 10523670 | pmc = 84849 | doi = 10.1128/mcb.19.11.7816 }}
• {{cite journal | vauthors = Youn HD, Grozinger CM, Liu JO | title = Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4 | journal = The Journal of Biological Chemistry | volume = 275 | issue = 29 | pages = 22563–7 | date = July 2000 | pmid = 10825153 | doi = 10.1074/jbc.C000304200 | doi-access = free }}
• {{cite journal | vauthors = Grozinger CM, Schreiber SL | title = Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 14 | pages = 7835–40 | date = July 2000 | pmid = 10869435 | pmc = 16631 | doi = 10.1073/pnas.140199597 | bibcode = 2000PNAS...97.7835G | doi-access = free }}
• {{cite journal | vauthors = Huynh KD, Fischle W, Verdin E, Bardwell VJ | title = BCoR, a novel corepressor involved in BCL-6 repression | journal = Genes & Development | volume = 14 | issue = 14 | pages = 1810–23 | date = July 2000 | pmid = 10898795 | pmc = 316791 | doi = 10.1101/gad.14.14.1810 }}
• {{cite journal | vauthors = Li J, Wang J, Wang J, Nawaz Z, Liu JM, Qin J, Wong J | title = Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3 | journal = The EMBO Journal | volume = 19 | issue = 16 | pages = 4342–50 | date = August 2000 | pmid = 10944117 | pmc = 302030 | doi = 10.1093/emboj/19.16.4342 }}
• {{cite journal | vauthors = Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP, Yang XJ | title = Regulation of histone deacetylase 4 by binding of 14-3-3 proteins | journal = Molecular and Cellular Biology | volume = 20 | issue = 18 | pages = 6904–12 | date = September 2000 | pmid = 10958686 | pmc = 88766 | doi = 10.1128/MCB.20.18.6904-6912.2000 }}
• {{cite journal | vauthors = Zhang CL, McKinsey TA, Lu JR, Olson EN | title = Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 1 | pages = 35–9 | date = January 2001 | pmid = 11022042 | doi = 10.1074/jbc.M007364200 | doi-access = free }}
• {{cite journal | vauthors = McKinsey TA, Zhang CL, Lu J, Olson EN | title = Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation | journal = Nature | volume = 408 | issue = 6808 | pages = 106–11 | date = November 2000 | pmid = 11081517 | doi = 10.1038/35040593 | pmc = 4459600 | bibcode = 2000Natur.408..106M }}
• {{cite journal | vauthors = Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA | title = Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 26 | pages = 14329–33 | date = December 2000 | pmid = 11114188 | pmc = 18918 | doi = 10.1073/pnas.250494697 | bibcode = 2000PNAS...9714329Z | doi-access = free }}
• {{cite journal | vauthors = McKinsey TA, Zhang CL, Olson EN | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 26 | pages = 14400–5 | date = December 2000 | pmid = 11114197 | pmc = 18930 | doi = 10.1073/pnas.260501497 | bibcode = 2000PNAS...9714400M | doi-access = free }}

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• {{MeshName|HDAC4+protein,+human}}

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Category:EC 3.5.1