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Phosphorylation of histone H1 by P-TEFb is a necessary step in skeletal muscle differentiation

Authors

  • Siobhan K. O'Brien,

    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School Worcester, Worcester, Massachusetts
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  • Kendall L. Knight,

    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School Worcester, Worcester, Massachusetts
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  • Tariq M. Rana

    Corresponding author
    1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School Worcester, Worcester, Massachusetts
    2. Program for RNA Biology, Sanford-Burnham Medical Research Institute, La Jolla, California
    • 0901 N, Torrey Pines Road, La Jolla, CA 92037.
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Abstract

Positive transcription elongation factor b (P-TEFb), the complex of Cyclin T1 and CDK9, activates the transcription of many viral and eukaryotic genes at the point of mRNA elongation. The activity of P-TEFb has been implicated in the differentiation of a number of cell types, including skeletal muscle. In order to promote transcription, P-TEFb hyperphosphorylates RNA Pol II, thereby increasing its processivity. Our previous work identified histone H1 as a P-TEFb substrate during HIV-1 and immediate-early transcription. Here, we examine the role of P-TEFb phosphorylation of histone H1 during differentiation, using the myoblast cell line C2C12 as a model for skeletal muscle differentiation. We found that H1 phosphorylation is elevated in differentiating C2C12, and this phosphorylation is sensitive to P-TEFb inhibition. H1 phosphorylation was also necessary for the induction of three muscle marker genes that require P-TEFb for expression. Additionally, ChIP experiments demonstrate that H1 dissociates from muscle differentiation marker genes in C2C12 cells under active P-TEFb conditions. We determine that both P-TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes. J. Cell. Physiol. 227: 383–389, 2012. © 2011 Wiley Periodicals, Inc.

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