SMYD1, the myogenic activator, is a direct target of serum response factor and myogenin.
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.
The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241. dlli@bio.ecnu.edu.cn
Dali
D
Li
Zhiyv
Z
Niu
Weishi
W
Yu
Yu
Y
Qian
Qian
Q
Wang
Qiang
Q
Li
Zhengfang
Z
Yi
Jian
J
Luo
Xiushan
X
Wu
Yuequn
Y
Wang
Robert J
RJ
Schwartz
Mingyao
M
Liu
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024721:E-Box Elements; D004622:Embryo, Mammalian / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D018008:Myogenin; C484340:SMYD1 protein, human; D026362:Serum Response Factor; C096485:Smyd1 protein, mouse; D014157:Transcription Factors