Hes6 regulates myogenic differentiation.
Hes6 is a basic helix-loop-helix transcription factor homologous to Drosophila Enhancer of Split (EoS) proteins. It is known to promote neural differentiation and to bind to Hes1, a related protein that is part of the Notch signalling pathway, affecting Hes1-regulated transcription. We show that Hes6 is expressed in the murine embryonic myotome and is induced on C2C12 myoblast differentiation in vitro. Hes6 binds DNA containing the Enhancer of Split E box (ESE) motif, the preferred binding site of Drosophila EoS proteins, and represses transcription of an ESE box reporter. When overexpressed in C2C12 cells, Hes6 impairs normal differentiation, causing a decrease in the induction of the cyclin-dependent kinase inhibitor, p21(Cip1), and an increase in the number of cells that can be recruited back into the cell cycle after differentiation in culture. In Xenopus embryos, Hes6 is co-expressed with MyoD in early myogenic development. Microinjection of Hes6 RNA in vivo in Xenopus embryos results in an expansion of the myotome, but suppression of terminal muscle differentiation and disruption of somite formation at the tailbud stage. Analysis of Hes6 mutants indicates that the DNA-binding activity of Hes6 is not essential for its myogenic phenotype, but that protein-protein interactions are. Thus, we demonstrate a novel role for Hes6 in multiple stages of muscle formation.
Cossins
Judy
J
Cancer Research UK, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Vernon
Ann E
AE
Zhang
Yun
Y
Philpott
Anna
A
Jones
Philip H
PH
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000235:genetics; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000196:embryology*; D009154:Mutation; D012097:Repressor Proteins; D019170:Somites / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014981:Xenopus; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C084530:E(spl)mdelta-HLH protein, Drosophila; C486570:Hes6 protein, mouse