Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Hdac4. (This text reflects annotations as of Tuesday, May 21, 2013.) MGI curation of this mouse gene is considered complete, including annotations derived from the biomedical literature as of September 10, 2009. If you know of any additional information regarding this mouse gene please let us know. Please supply mouse gene symbol and a PubMed ID.

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] 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. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Hdac4
  • participates in the following biological processes:
    • negative regulation of cell proliferation ^[17]
    • negative regulation of transcription from RNA polymerase II promoter ^[6]
    • negative regulation of transcription, DNA-dependent ^[7]
    • protein deacetylation ^[8]
  • performs the following molecular functions:
    • DNA binding ^[7]
    • protein deacetylase activity ^[8]
  • is located in the following cellular components:
    • actomyosin ^[8]
    • cytosol ^[9]
    • neuromuscular junction ^[6]
• The gene product of Hdac4 has been shown to bind to the gene products of Cmtm2a, Dnajb5, Dnajb6, Gsc, Hdac5, Myocd, Runx2, Smad3. ^{[1, 3, 5, 7, 10, 11, 12, 14, 17]} Researchers have inferred, based on physical interactions, that the gene product of Hdac4
  • performs the following molecular functions:
    • protein kinase binding ^[4]
    • transcription factor binding ^[13]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Hdac4
  • participates in the following biological processes:
    • negative regulation of cell proliferation ^[17]
    • negative regulation of glycolysis ^[16]
    • negative regulation of osteoblast differentiation ^[12]
    • negative regulation of transcription, DNA-dependent ^[11]
    • osteoblast development ^[12]
    • positive regulation of transcription from RNA polymerase II promoter ^[16]
    • positive regulation of transcription, DNA-dependent ^[16]
    • regulation of cardiac muscle contraction by calcium ion signaling ^[8]
    • response to denervation involved in regulation of muscle adaptation ^[16]
    • skeletal system development ^[17]
  • is located in the following cellular components:
    • cytoplasm ^[16]
    • nucleus ^[16]
• Researchers have inferred, based on genetic interactions, that the gene product of Hdac4
  • participates in the following biological processes:
    • negative regulation of transcription from RNA polymerase II promoter based on interactions with Mef2c, Myocd, Runx2, Tgfb1 ^{[2, 5, 12, 17]}
    • regulation of skeletal muscle fiber development based on interactions with Hdac5, Hdac9 ^[15]
    • regulation of striated muscle cell differentiation based on interactions with Hdac5, Hdac9 ^[15]
  • performs the following molecular functions:
    • transcription corepressor activity based on interactions with Smad3 ^[12]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Hdac4:
  • participates in the following biological processes:
    • chromatin remodeling
    • histone deacetylation
    • histone H3 deacetylation
    • histone H4 deacetylation
    • negative regulation of myotube differentiation
    • negative regulation of sequence-specific DNA binding transcription factor activity
    • negative regulation of transcription from RNA polymerase II promoter
    • negative regulation of transcription, DNA-dependent
    • peptidyl-lysine deacetylation
    • positive regulation of cell proliferation
    • positive regulation of protein sumoylation
    • positive regulation of sequence-specific DNA binding transcription factor activity
    • positive regulation of transcription from RNA polymerase II promoter
    • regulation of protein binding
    • response to drug
    • response to interleukin-1
  • performs the following molecular functions:
    • activating transcription factor binding
    • core promoter binding
    • histone deacetylase activity
    • histone deacetylase binding
    • potassium ion binding
    • protein deacetylase activity
    • repressing transcription factor binding
    • sequence-specific DNA binding
    • transcription factor binding
    • transcription regulatory region DNA binding
    • zinc ion binding
  • is located in the following cellular components:
    • A band
    • cytoplasm
    • cytosol
    • histone deacetylase complex
    • nucleus
    • protein complex
    • sarcomere
    • transcriptional repressor complex
    • Z disc

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Summary text based on GO annotations supported by structural data

• Hdac4 encodes a protein or proteins that contain the following InterPro domains: Histone deacetylase class II, eukaryotic, Histone deacetylase domain, Histone deacetylase superfamily, Histone deacetylase, glutamine rich N-terminal domain, indicating that the gene product:
  • participates in the following biological processes:
    • chromatin modification

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Hdac4 indicates that it:
  • participates in the following biological processes:
    • chromatin modification
    • regulation of transcription, DNA-dependent
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • hydrolase activity
    • metal ion binding
• Hdac4 has been associated with the Enzyme Commission numbers: 3.5.1.98, which implies that the gene product:
  • participates in the following biological processes:
    • histone H3 deacetylation
    • histone H4 deacetylation
  • performs the following molecular functions:
    • histone deacetylase activity (H3-K14 specific)
    • histone deacetylase activity (H3-K9 specific)
    • histone deacetylase activity (H4-K16 specific)
    • NAD-dependent histone deacetylase activity (H3-K14 specific)
    • NAD-dependent histone deacetylase activity (H3-K9 specific)
    • NAD-dependent histone deacetylase activity (H4-K16 specific)

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References

1. Ago T et al. (2008) A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell, 133:978-93. (PubMed:18555775)
2. Arnold MA et al. (2007) MEF2C transcription factor controls chondrocyte hypertrophy and bone development. Dev Cell, 12:377-89. (PubMed:17336904)
3. Backs J et al. (2008) Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II responsiveness by oligomerization with histone deacetylase 4. Mol Cell Biol, 28:3437-45. (PubMed:18332106)
4. Berdeaux R et al. (2007) SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med, 13:597-603. (PubMed:17468767)
5. Cao D et al. (2005) Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin. Mol Cell Biol, 25:364-76. (PubMed:15601857)
6. Cohen TJ et al. (2007) The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. J Biol Chem, 282:33752-9. (PubMed:17873280)
7. Dai YS et al. (2005) The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol, 25:9936-48. (PubMed:16260608)
8. Gupta MP et al. (2008) HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity. J Biol Chem, 283:10135-46. (PubMed:18250163)
9. Heverin M et al. (2007) Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. Arterioscler Thromb Vasc Biol, 27:2191-7. (PubMed:17761942)
10. Izzi L et al. (2007) Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development. EMBO J, 26:3132-43. (PubMed:17568773)
11. Jeong BC et al. (2004) Androgen receptor corepressor-19 kDa (ARR19), a leucine-rich protein that represses the transcriptional activity of androgen receptor through recruitment of histone deacetylase. Mol Endocrinol, 18:13-25. (PubMed:14576337)
12. Kang JS et al. (2005) Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J, 24:2543-55. (PubMed:15990875)
13. Lemercier C et al. (2000) mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity. J Biol Chem, 275:15594-9. (PubMed:10748098)
14. Pan Z et al. (2008) Impaired placental trophoblast lineage differentiation in Alkbh1(-/-) mice. Dev Dyn, 237:316-27. (PubMed:18163532)
15. Potthoff MJ et al. (2007) Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Invest, 117:2459-67. (PubMed:17786239)
16. Tang H et al. (2009) A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression. Mol Biol Cell, 20:1120-31. (PubMed:19109424)
17. Vega RB et al. (2004) Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell, 119:555-66. (PubMed:15537544)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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