SMYD1, the myogenic activator, is a direct target of serum response factor and myogenin

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.

Histone Methyltransferase SETD3 Regulates Muscle Differentiation

“…Collectively, these findings demonstrate that SETD3 exerts specific HMTase activity in the mono-and dimethylation of H3K4 and H3K36 under both in vitro and in vivo conditions. SETD3 Induces Transcriptional Activation-It was noted previously that histone H3K4 HMTase SMYD1 functions as a transcription activator, playing an essential role in myogenesis and cardiogenesis in different species (6,(25)(26)(27). To determine whether or not methylation of H3K4 and H3K36 by SETD3 can be attributed to a general transcription activation effect similar to that of SMYD1, we conducted a transient transfection assay using the CMX-GAL4-SV40 reporter system.…”

“…A recent report suggesting that SMYD1 expression is regulated by serum response factor as well as myogenin further suggests the role of a complex transcriptional network in myogenesis (26). Amino acid sequence alignment between SMYD1 and SETD3 SET domains shows very low similarity (15%) between these two methyltransferases.…”

Identification and Characterization of Genes Related to the Development of Skeletal Muscle in the Hainan Black Goat

“…The high expression of myogenin can promote the differentiation of myoblasts and the form of the myotube, and hence SMYD1 is regarded as a key regulator gene in controlling the development of skeletal muscle. 25) RBM26 is a multi-purpose gene, and the homologous gene RBM4 is highly expressed in skeletal muscle and cardiac muscle. 26) RBM4 has multiple roles in mRNA metabolism and translation control.…”

GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor Signaling

“…Chromatin Immunoprecipitation Assay-ChIP was performed as described (33). Briefly, HMEC-1 cells growing in 10-cm dishes were treated with formaldehyde, and the DNAprotein complex was extracted.…”