HDAC4

Last updated
HDAC4
2vqj.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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:

See also

Related Research Articles

<span class="mw-page-title-main">HDAC1</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

<span class="mw-page-title-main">Nuclear receptor co-repressor 1</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the NCOR1 gene.

<span class="mw-page-title-main">Nuclear receptor co-repressor 2</span> Protein-coding gene in the species Homo sapiens

The nuclear receptor co-repressor 2 (NCOR2) is a transcriptional coregulatory protein that contains several nuclear receptor-interacting domains. In addition, NCOR2 appears to recruit histone deacetylases to DNA promoter regions. Hence NCOR2 assists nuclear receptors in the down regulation of target gene expression. NCOR2 is also referred to as a silencing mediator for retinoid or thyroid-hormone receptors (SMRT) or T3 receptor-associating cofactor 1 (TRAC-1).

<span class="mw-page-title-main">Histone deacetylase 2</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.

<span class="mw-page-title-main">HDAC3</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 3 is an enzyme encoded by the HDAC3 gene in both humans and mice.

<span class="mw-page-title-main">SIN3A</span> Protein-coding gene in the species Homo sapiens

Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.

<span class="mw-page-title-main">RBBP4</span> Protein-coding gene in the species Homo sapiens

Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.

<span class="mw-page-title-main">MEF2C</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family.

<span class="mw-page-title-main">HDAC6</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene. HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.

<span class="mw-page-title-main">Testicular receptor 2</span> Human protein-coding gene

The testicular receptor 2 (TR2) also known as NR2C1 is protein that in humans is encoded by the NR2C1 gene. TR2 is a member of the nuclear receptor family of transcription factors.

<span class="mw-page-title-main">CTBP1</span> Protein-coding gene in the species Homo sapiens

C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene. CtBP1 is one of two CtBP proteins, the other protein being CtBP2.

<span class="mw-page-title-main">Myocyte-specific enhancer factor 2A</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2A is a protein that in humans is encoded by the MEF2A gene. MEF2A is a transcription factor in the Mef2 family. In humans it is located on chromosome 15q26. Certain mutations in MEF2A cause an autosomal dominant form of coronary artery disease and myocardial infarction.

<span class="mw-page-title-main">Histone deacetylase 5</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 5 is an enzyme that in humans is encoded by the HDAC5 gene.

<span class="mw-page-title-main">HDAC9</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 9 is an enzyme that in humans is encoded by the HDAC9 gene.

<span class="mw-page-title-main">MEF2D</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2D is a protein that in humans is encoded by the MEF2D gene.

<span class="mw-page-title-main">HDAC7</span>

Histone deacetylase 7 is an enzyme that in humans is encoded by the HDAC7 gene.

<span class="mw-page-title-main">SAP30</span> Protein-coding gene in the species Homo sapiens

Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.

<span class="mw-page-title-main">SIN3B</span> Protein-coding gene in the species Homo sapiens

Paired amphipathic helix protein Sin3b is a protein that in humans is encoded by the SIN3B gene.

<span class="mw-page-title-main">CABIN1</span> Protein-coding gene in the species Homo sapiens

Calcineurin-binding protein cabin-1 is a protein that in humans is encoded by the CABIN1 gene.

<span class="mw-page-title-main">TBL1X</span> Protein-coding gene in the species Homo sapiens

Transducin (beta)-like 1X-linked, also known as TBL1X, is a protein which in humans is encoded by the TBL1X gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000068024 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 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. 1 2 3 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. 1 2 3 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. 1 2 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. 1 2 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

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