The winged-helix/forkhead protein myocyte nuclear factor beta (MNF-beta) forms a co-repressor complex with mammalian sin3B.
Winged-helix/forkhead proteins regulate developmental events in both invertebrate and vertebrate organisms, but biochemical functions that establish a mechanism of action have been defined for only a few members of this extensive gene family. Here we demonstrate that MNF (myocyte nuclear factor)-beta, a winged-helix protein expressed selectively and transiently in myogenic precursor cells of the heart and skeletal muscles, collaborates with proteins of the mammalian Sin3 (mSin3) family to repress transcription. Mutated forms of MNF-beta that fail to bind mSin3 are defective in transcriptional repression and in negative growth regulation, an overexpression phenotype revealed in oncogenic transformation assays. These data extend the known repertoire of transcription factors with which mSin3 proteins can function as co-repressors to include members of the winged-helix gene family. Transcriptional repression by MNF-beta-mSin3 complexes may contribute to the co-ordination of cellular proliferation and terminal differentiation of myogenic precursor cells.
Yang
Q
Q
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., NB11.200, Dallas, TX 75390-8573, USA.
Kong
Y
Y
Rothermel
B
B
Garry
D J
DJ
Bassel-Duby
R
R
Williams
R S
RS
D017500:Adenovirus E1A Proteins; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D016147:Genes, Tumor Suppressor; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000166:cytology; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D018631:ras Proteins
D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C497672:Foxk1 protein, mouse; D009687:Nuclear Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D012097:Repressor Proteins; C115812:Sin3b protein, mouse; D014157:Transcription Factors; D018631:ras Proteins