HDAC4

Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the HDAC4 gene.[5][6]

HDAC4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesHDAC4, AHO3, BDMR, HA6116, HD4, HDAC-4, HDAC-A, HDACA, histone deacetylase 4, NEDCHID
External IDsOMIM: 605314 MGI: 3036234 HomoloGene: 55946 GeneCards: HDAC4
Orthologs
SpeciesHumanMouse
Entrez

9759

208727

Ensembl

ENSG00000068024

ENSMUSG00000026313

UniProt

P56524

Q6NZM9

RefSeq (mRNA)

NM_006037
NM_001378414
NM_001378415
NM_001378416
NM_001378417

NM_207225

RefSeq (protein)

NP_006028
NP_001365343
NP_001365344
NP_001365345
NP_001365346

NP_997108

Location (UCSC)Chr 2: 239.05 – 239.4 MbChr 1: 91.86 – 92.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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:

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000068024 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000026313 - 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. 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.
  6. 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.
  7. "Entrez Gene: HDAC4 histone deacetylase 4".
  8. 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.
  9. Protein for Sight, Scientific American, 300, 3 (March 2009), p. 23
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. 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.
  27. 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.
  28. 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

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