HDAC4

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, NEDCHID
External IDs	OMIM: 605314; MGI: 3036234; HomoloGene: 55946; GeneCards: HDAC4; OMA:HDAC4 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q37.3 Start 239,048,168 bp[1] End 239,401,654 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1|1 D Start 91,856,501 bp[2] End 92,123,421 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve glutes gastrocnemius muscle tibialis anterior muscle muscle of thigh muscle layer of sigmoid colon endothelial cell deltoid muscle Skeletal muscle tissue of biceps brachii blood Top expressed in otic vesicle granulocyte gastrula Rostral migratory stream dentate gyrus of hippocampal formation granule cell muscle of thigh lip interventricular septum muscle tissue skeletal muscle tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function NAD-dependent histone deacetylase activity (H3-K14 specific) sequence-specific DNA binding DNA binding transcription corepressor activity histone deacetylase activity zinc ion binding transcription factor binding histone deacetylase binding potassium ion binding chromatin binding metal ion binding protein binding protein kinase binding hydrolase activity protein deacetylase activity identical protein binding promoter-specific chromatin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding SUMO transferase activity Cellular component cytoplasm histone deacetylase complex neuromuscular junction transcription repressor complex sarcomere Z discdkac A band actomyosin nucleus cytosol nucleoplasm protein-containing complex Biological process positive regulation of reactive oxygen species biosynthetic process histone H3 deacetylation skeletal system development chromatin remodeling peptidyl-lysine deacetylation regulation of cardiac muscle contraction by calcium ion signaling negative regulation of glycolytic process response to interleukin-1 regulation of transcription, DNA-templated regulation of gene expression, epigenetic cellular response to tumor necrosis factor positive regulation of DNA-binding transcription factor activity negative regulation of transcription by RNA polymerase II positive regulation of protein sumoylation negative regulation of DNA-binding transcription factor activity negative regulation of osteoblast differentiation transcription, DNA-templated nervous system development regulation of striated muscle cell differentiation positive regulation of transcription, DNA-templated positive regulation of smooth muscle cell migration B cell activation histone H4 deacetylation cellular response to mechanical stimulus positive regulation of neuron apoptotic process cardiac muscle hypertrophy in response to stress positive regulation of cell population proliferation negative regulation of myotube differentiation response to denervation involved in regulation of muscle adaptation regulation of skeletal muscle fiber development osteoblast development B cell differentiation cellular response to parathyroid hormone stimulus inflammatory response positive regulation of lamellipodium assembly regulation of protein binding negative regulation of transcription, DNA-templated histone deacetylation positive regulation of transcription by RNA polymerase II negative regulation of cell population proliferation positive regulation of smooth muscle cell proliferation chromatin organization negative regulation of pri-miRNA transcription by RNA polymerase II protein deacetylation protein sumoylation positive regulation of male mating behavior Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 1: 91.86 – 92.12 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

• Histone deacetylase

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

• 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

• HDAC4+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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