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

GO curators for mouse genes have assigned the following annotations to the gene product of Mef2a. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a DNA-binding transcription factor that activates many muscle-specific, growth factor-induced, and stress-induced genes. The encoded protein can act as a homodimer or as a heterodimer and is involved in several cellular processes, including muscle development, neuronal differentiation, cell growth control, and apoptosis. Defects in this gene could be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

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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 Mef2a
  • participates in the following biological processes:
    • positive regulation of transcription, DNA-dependent ^[5]
    • regulation of transcription, DNA-dependent ^{[3, 8]}
  • performs the following molecular functions:
    • chromatin binding ^{[4, 12, 16]}
    • DNA binding ^{[3, 9]}
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription ^[4]
    • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity ^[16]
    • sequence-specific DNA binding ^[7]
    • sequence-specific DNA binding transcription factor activity ^{[3, 8]}
  • is located in the following cellular components:
    • nuclear chromatin ^[2]
    • nucleus ^{[9, 10, 12, 14, 17]}
• The gene product of Mef2a has been shown to bind to the gene products of Klf15, Nfix. ^{[5, 11]} Researchers have inferred, based on physical interactions, that the gene product of Mef2a
  • performs the following molecular functions:
    • activating transcription factor binding ^[14]
    • protein kinase binding ^[15]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Mef2a
  • participates in the following biological processes:
    • cardiac conduction ^[13]
    • mitochondrial genome maintenance ^[13]
    • mitochondrion distribution ^[13]
    • ventricular cardiac myofibril development ^[13]
• Researchers have inferred, based on genetic interactions, that the gene product of Mef2a
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Ascl1, Myog, Tcf3 ^{[1, 6]}
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Mef2a
  • is located in the following cellular components:
    • nucleus ^[8]

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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 Mef2a:
  • participates in the following biological processes:
    • cellular response to calcium ion
    • ERK5 cascade
    • MAPK cascade
    • negative regulation of transcription from RNA polymerase II promoter
    • positive regulation of transcription from RNA polymerase II promoter
    • transcription from RNA polymerase II promoter
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • activating transcription factor binding
    • histone acetyltransferase binding
    • histone deacetylase binding
    • protein heterodimerization activity
    • RNA polymerase II regulatory region sequence-specific DNA binding
    • RNA polymerase II transcription coactivator activity
    • RNA polymerase II transcription factor binding
    • sequence-specific DNA binding
    • sequence-specific DNA binding RNA polymerase II transcription factor activity
    • sequence-specific DNA binding transcription factor activity
    • SMAD binding
  • is located in the following cellular components:
    • nucleus

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Summary text based on GO annotations supported by structural data

• Mef2a encodes a protein or proteins that contain the following InterPro domains: Holliday junction regulator protein family C-terminal, Transcription factor, MADS-box, indicating that the gene product:
  • performs the following molecular functions:
    • protein dimerization activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Mef2a indicates that it:
  • participates in the following biological processes:
    • apoptotic process
    • cell differentiation
    • multicellular organismal development
    • nervous system development

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References

1. Black BL et al. (1996) Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family. J Biol Chem, 271:26659-63. (PubMed:8900141)
2. Choi J et al. (2010) Histone demethylase LSD1 is required to induce skeletal muscle differentiation by regulating myogenic factors. Biochem Biophys Res Commun, 401:327-32. (PubMed:20833138)
3. Di Lisi R et al. (1998) Combinatorial cis-acting elements control tissue-specific activation of the cardiac troponin I gene in vitro and in vivo. J Biol Chem, 273:25371-80. (PubMed:9738004)
4. Durham JT et al. (2006) Myospryn is a direct transcriptional target for MEF2A that encodes a striated muscle, alpha-actinin-interacting, costamere-localized protein. J Biol Chem, 281:6841-9. (PubMed:16407236)
5. Gray S et al. (2002) The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose transporter GLUT4. J Biol Chem, 277:34322-8. (PubMed:12097321)
6. Jung SY et al. (2010) TRIM72, a novel negative feedback regulator of myogenesis, is transcriptionally activated by the synergism of MyoD (or myogenin) and MEF2. Biochem Biophys Res Commun, 396:238-45. (PubMed:20399744)
7. Komuro I et al. (1993) Gtx: a novel murine homeobox-containing gene, expressed specifically in glial cells of the brain and germ cells of testis, has a transcriptional repressor activity in vitro for a serum-inducible promoter. EMBO J, 12:1387-401. (PubMed:8096811)
8. Lazaro JB et al. (2002) Cyclin D-cdk4 activity modulates the subnuclear localization and interaction of MEF2 with SRC-family coactivators during skeletal muscle differentiation. Genes Dev, 16:1792-805. (PubMed:12130539)
9. Lemonnier M et al. (2004) Characterization of a cardiac-specific enhancer, which directs {alpha}-cardiac actin gene transcription in the mouse adult heart. J Biol Chem, 279:55651-8. (PubMed:15491989)
10. Lin X et al. (1996) The expression of MEF2 genes is implicated in CNS neuronal differentiation. Brain Res Mol Brain Res, 42:307-16. (PubMed:9013788)
11. Messina G et al. (2010) Nfix regulates fetal-specific transcription in developing skeletal muscle. Cell, 140:554-66. (PubMed:20178747)
12. Mukwevho E et al. (2008) Caffeine induces hyperacetylation of histones at the MEF2 site on the Glut4 promoter and increases MEF2A binding to the site via a CaMK-dependent mechanism. Am J Physiol Endocrinol Metab, 294:E582-8. (PubMed:18198354)
13. Naya FJ et al. (2002) Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor. Nat Med, 8:1303-9. (PubMed:12379849)
14. Quinn ZA et al. (2001) Smad proteins function as co-modulators for MEF2 transcriptional regulatory proteins. Nucleic Acids Res, 29:732-42. (PubMed:11160896)
15. Satoh K et al. (2007) Nemo-like kinase-myocyte enhancer factor 2A signaling regulates anterior formation in Xenopus development. Mol Cell Biol, 27:7623-30. (PubMed:17785444)
16. Schlesinger J et al. (2011) The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs. PLoS Genet, 7:e1001313. (PubMed:21379568)
17. Yamaguchi N et al. (2007) Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac muscle Ca release channel. J Clin Invest, 117:1344-53. (PubMed:17431507)

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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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