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PMID:19783823

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Citation

Li, D, Niu, Z, Yu, W, Qian, Y, Wang, Q, Li, Q, Yi, Z, Luo, J, Wu, X, Wang, Y, Schwartz, RJ and Liu, M (2009) SMYD1, the myogenic activator, is a direct target of serum response factor and myogenin. Nucleic Acids Res. 37:7059-71

Abstract

SMYD1 is a heart and muscle specific SET-MYND domain containing protein, which functions as a histone methyltransferase and regulates downstream gene transcription. We demonstrated that the expression of SMYD1 is restricted in the heart and skeletal muscle tissues in human. To reveal the regulatory mechanisms of SMYD1 expression during myogenesis and cardiogenesis, we cloned and characterized the human SMYD1 promoter, which contains highly conserved serum response factor (SRF) and myogenin binding sites. Overexpression of SRF and myogenin significantly increased the endogenous expression level of Smyd1 in C2C12 cells, respectively. Deletion of Srf in the heart of mouse embryos dramatically decreased the expression level of Smyd1 mRNA and the expression of Smyd1 can be rescued by exogenous SRF introduction in SRF null ES cells during differentiation. Furthermore, we demonstrated that SRF binds to the CArG site and myogenin binds to the E-box element on Smyd1 promoter region using EMSA and ChIP assays. Moreover, forced expression of SMYD1 accelerates myoblast differentiation and myotube formation in C2C12 cells. Taken together, these studies demonstrated that SMYD1 is a key regulator of myogenic differentiation and acts as a downstream target of muscle regulatory factors, SRF and myogenin.

Links

PubMed PMC2790895 Online version:10.1093/nar/gkp773

Keywords

Animals; Binding Sites; Cell Differentiation; Cell Line; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; E-Box Elements; Embryo, Mammalian/metabolism; Humans; Mice; Mice, Knockout; Muscle Development; Muscle Proteins/chemistry; Muscle Proteins/genetics; Muscle Proteins/metabolism; Muscle, Skeletal/metabolism; Myocardium/metabolism; Myogenin/metabolism; Promoter Regions, Genetic; Protein Structure, Tertiary; Serum Response Factor/genetics; Serum Response Factor/metabolism; Transcription Factors/chemistry; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SRF

involved_in

GO:0003257: positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:Q9JM73

P

Seeded From UniProt

complete

MOUSE:MYOG

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:MYOG

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000305: curator inference used in manual assertion

GO:0000977

F

Seeded From UniProt

complete

MOUSE:MYOG

enables

GO:0070888: E-box binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001158)

Seeded From UniProt

complete

MOUSE:MYOG

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000305: curator inference used in manual assertion

GO:0000977

P

Seeded From UniProt

complete

HUMAN:MYOG

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:MYOG

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMYD1

involved_in

GO:0010831: positive regulation of myotube differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMYD1

involved_in

GO:0045663: positive regulation of myoblast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SRF

involved_in

GO:0003257: positive regulation of transcription from RNA polymerase II promoter involved in myocardial precursor cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SRF

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0000167)

Seeded From UniProt

complete

MOUSE:SRF

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:SRF

enables

GO:0001228: DNA-binding transcription activator activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0001952)

Seeded From UniProt

complete

MOUSE:SRF

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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