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During embryogenesis, differentiation of skeletal muscle isregulated by transcription factors that include members of theMsx homeoprotein family. By investigating Msx1 function in repressionof myogenic gene expression, we identified a physical interactionbetween Msx1 and H1b, a specific isoform of mouse histone H1.We found that Msx1 and H1b bind to a key regulatory elementof MyoD, a central regulator of skeletal muscle differentiation,where they induce repressed chromatin. Moreover, Msx1 and H1bcooperate to inhibit muscle differentiation in cell cultureand in Xenopus animal caps. Our findings define a previouslyunknown function for "linker" histones in gene-specific transcriptionalregulation.
1 Center for Advanced Biotechnology and Medicine, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. 2 The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. 3 Department of Medicine, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. 4 Department of Neuroscience, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. 5 Department of Biochemistry, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
* To whom correspondence should be addressed. E-mail: abate{at}cabm.rutgers.edu
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