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Histone deacetylase 4
Catalytic domain of HDAC4 with bound inhibitor. PDB rendering based on 2vqj[1].
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols HDAC4 ; AHO3; BDMR; HA6116; HD4; HDAC-4; HDAC-A; HDACA
External IDs OMIM605314 MGI3036234 HomoloGene55946 ChEMBL: 3524 GeneCards: HDAC4 Gene
EC number
RNA expression pattern
PBB GE HDAC4 204225 at tn.png
More reference expression data
Species Human Mouse
Entrez 9759 208727
Ensembl ENSG00000068024 ENSMUSG00000026313
UniProt P56524 Q6NZM9
RefSeq (mRNA) NM_006037 NM_207225
RefSeq (protein) NP_006028 NP_997108
Location (UCSC) Chr 2:
239.97 – 240.32 Mb
Chr 1:
91.93 – 92.15 Mb
PubMed search [1] [2]

Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.[2][3]


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.[4] Furthermore, HDAC4 is required for TGFbeta1-induced myofibroblastic differentiation.[5]

Clinical significance[edit]

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.[6][7]

See also[edit]


HDAC4 has been shown to interact with MEF2C,[8][9] Zinc finger and BTB domain-containing protein 16,[10][11] BCL6,[11] CBX5,[12] MAPK3,[13] Testicular receptor 2,[14][15] MAPK1,[13] Myocyte-specific enhancer factor 2A,[16][17] Nuclear receptor co-repressor 1,[18][19] Nuclear receptor co-repressor 2,[18][19] YWHAB,[20] HDAC3,[2][18][20][21] GATA1,[22]BTG2,[23] and YWHAE.[20][24]


  1. ^ Bottomley, M. J.; Lo Surdo, P.; Di Giovine, P.; Cirillo, A.; Scarpelli, R.; Ferrigno, F.; Jones, P.; Neddermann, P.; De Francesco, R.; Steinkühler, C.; Gallinari, P.; Carfí, A. (2008). "Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain". Journal of Biological Chemistry 283 (39): 26694–26704. doi:10.1074/jbc.M803514200. PMC 3258910. PMID 18614528.  edit
  2. ^ a b Grozinger CM, Hassig CA, Schreiber SL (April 1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4868–73. doi:10.1073/pnas.96.9.4868. PMC 21783. PMID 10220385. 
  3. ^ 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". J. Biol. Chem. 274 (17): 11713–20. doi:10.1074/jbc.274.17.11713. PMID 10206986. 
  4. ^ "Entrez Gene: HDAC4 histone deacetylase 4". 
  5. ^ Glenisson W, Castronovo V, Waltregny D. (October 2007). "Histone deacetylase 4 is required for TGFbeta1-induced myofibroblastic differentiation.". Biochim Biophys Acta. 1773 (10): 1572–82. doi:10.1016/j.bbamcr.2007.05.016. PMID 17610967. 
  6. ^ Protein for Sight, Scientific American, 300, 3 (March 2009), p. 23
  7. ^ 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. 
  8. ^ Wang, A H; Bertos N R; Vezmar M; Pelletier N; Crosato M; Heng H H; Th'ng J; Han J; Yang X J (November 1999). "HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7816–27. ISSN 0270-7306. PMC 84849. PMID 10523670. 
  9. ^ Wang, A H; Yang X J (September 2001). "Histone deacetylase 4 possesses intrinsic nuclear import and export signals". Mol. Cell. Biol. (United States) 21 (17): 5992–6005. doi:10.1128/MCB.21.17.5992-6005.2001. ISSN 0270-7306. PMC 87317. PMID 11486037. 
  10. ^ Chauchereau, Anne; Mathieu Marion, de Saintignon Julie, Ferreira Roger, Pritchard Linda L, Mishal Zohair, Dejean Anne, Harel-Bellan Annick (November 2004). "HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF". Oncogene (England) 23 (54): 8777–84. doi:10.1038/sj.onc.1208128. ISSN 0950-9232. PMID 15467736. 
  11. ^ a b Lemercier, Claudie; Brocard Marie-Paule, Puvion-Dutilleul Francine, Kao Hung-Ying, Albagli Olivier, Khochbin Saadi (June 2002). "Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor". J. Biol. Chem. (United States) 277 (24): 22045–52. doi:10.1074/jbc.M201736200. ISSN 0021-9258. PMID 11929873. 
  12. ^ Zhang, Chun Li; McKinsey Timothy A; Olson Eric N (October 2002). "Association of class II histone deacetylases with heterochromatin protein 1: potential role for histone methylation in control of muscle differentiation". Mol. Cell. Biol. (United States) 22 (20): 7302–12. doi:10.1128/MCB.22.20.7302-7312.2002. ISSN 0270-7306. PMC 139799. PMID 12242305. 
  13. ^ a b Zhou, X; Richon V M; Wang A H; Yang X J; Rifkind R A; Marks P A (December 2000). "Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (26): 14329–33. doi:10.1073/pnas.250494697. ISSN 0027-8424. PMC 18918. PMID 11114188. 
  14. ^ Franco, Peter J; Li Guangjin; Wei Li-Na (August 2003). "Interaction of nuclear receptor zinc finger DNA binding domains with histone deacetylase". Mol. Cell. Endocrinol. (Ireland) 206 (1-2): 1–12. doi:10.1016/S0303-7207(03)00254-5. ISSN 0303-7207. PMID 12943985. 
  15. ^ Franco, P J; Farooqui M; Seto E; Wei L N (August 2001). "The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases". Mol. Endocrinol. (United States) 15 (8): 1318–28. doi:10.1210/mend.15.8.0682. ISSN 0888-8809. PMID 11463856. 
  16. ^ Miska, E A; Karlsson C; Langley E; Nielsen S J; Pines J; Kouzarides T (September 1999). "HDAC4 deacetylase associates with and represses the MEF2 transcription factor". EMBO J. (ENGLAND) 18 (18): 5099–107. doi:10.1093/emboj/18.18.5099. ISSN 0261-4189. PMC 1171580. PMID 10487761. 
  17. ^ Lemercier, C; Verdel A; Galloo B; Curtet S; Brocard M P; Khochbin S (May 2000). "mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity". J. Biol. Chem. (UNITED STATES) 275 (20): 15594–9. doi:10.1074/jbc.M908437199. ISSN 0021-9258. PMID 10748098. 
  18. ^ a b c Fischle, Wolfgang; Dequiedt Franck; Hendzel Michael J; Guenther Matthew G; Lazar Mitchell A; Voelter Wolfgang; Verdin Eric (January 2002). "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR". Mol. Cell (United States) 9 (1): 45–57. doi:10.1016/S1097-2765(01)00429-4. ISSN 1097-2765. PMID 11804585. 
  19. ^ a b Huang, E Y; Zhang J; Miska E A; Guenther M G; Kouzarides T; Lazar M A (January 2000). "Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway". Genes Dev. (UNITED STATES) 14 (1): 45–54. ISSN 0890-9369. PMC 316335. PMID 10640275. 
  20. ^ a b c Grozinger, C M; Schreiber S L (July 2000). "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (14): 7835–40. doi:10.1073/pnas.140199597. ISSN 0027-8424. PMC 16631. PMID 10869435. 
  21. ^ Fischle, W; Dequiedt F; Fillion M; Hendzel M J; Voelter W; Verdin E (September 2001). "Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo". J. Biol. Chem. (United States) 276 (38): 35826–35. doi:10.1074/jbc.M104935200. ISSN 0021-9258. PMID 11466315. 
  22. ^ Watamoto, Kouichi; Towatari Masayuki; Ozawa Yukiyasu; Miyata Yasuhiko; Okamoto Mitsunori; Abe Akihiro; Naoe Tomoki; Saito Hidehiko (December 2003). "Altered interaction of HDAC5 with GATA-1 during MEL cell differentiation". Oncogene (England) 22 (57): 9176–84. doi:10.1038/sj.onc.1206902. ISSN 0950-9232. PMID 14668799. 
  23. ^ 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 J. 21 (9): 2215–25. doi:10.1096/fj.06-7548com. PMID 17371797. 
  24. ^ Miska, E A; Langley E; Wolf D; Karlsson C; Pines J; Kouzarides T (August 2001). "Differential localization of HDAC4 orchestrates muscle differentiation". Nucleic Acids Res. (England) 29 (16): 3439–47. doi:10.1093/nar/29.16.3439. PMC 55849. PMID 11504882. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.