title: Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb1.
abstract: Skeletal myogenesis is precisely regulated by multiple transcription factors. Previously, we demonstrated that enhancer of polycomb 1 (Epc1) induces skeletal muscle differentiation by potentiating serum response factor (SRF)-dependent muscle gene activation. Here, we report that an interacting partner of Epc1, ret finger protein (RFP), blocks skeletal muscle differentiation. Our findings show that RFP was highly expressed in skeletal muscles and was downregulated during myoblast differentiation. Forced expression of RFP delayed myoblast differentiation, whereas knockdown enhanced it. Epc1-induced enhancements of SRF-dependent multinucleation, transactivation of the skeletal α-actin promoter, binding of SRF to the serum response element, and muscle-specific gene induction were blocked by RFP. RFP interfered with the physical interaction between Epc1 and SRF. Muscles from rfp knockout mice (Rfp(-/-)) mice were bigger than those from wild-type mice, and the expression of SRF-dependent muscle-specific genes was upregulated. Myotube formation and myoblast differentiation were enhanced in Rfp(-/-) mice. Taken together, our findings highlight RFP as a novel regulator of muscle differentiation that acts by modulating the expression of SRF-dependent skeletal muscle-specific genes.
authors.affiliation: Department of Pharmacology and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kee
authors.forename: J-R
authors.initials: JR
authors.lastname: Kim
authors.forename: H
authors.initials: H
authors.lastname: Joung
authors.forename: N
authors.initials: N
authors.lastname: Choe
authors.forename: S E
authors.initials: SE
authors.lastname: Lee
authors.forename: G H
authors.initials: GH
authors.lastname: Eom
authors.forename: J C
authors.initials: JC
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Geyer
authors.forename: M
authors.initials: M
authors.lastname: Jijiwa
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Kawai
authors.forename: W J
authors.initials: WJ
authors.lastname: Weninger
authors.forename: S B
authors.initials: SB
authors.lastname: Seo
authors.forename: K-I
authors.initials: KI
authors.lastname: Nam
authors.forename: M H
authors.initials: MH
authors.lastname: Jeong
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Kook
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C496700:Epc1 protein, mouse; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins