Phosphorylation of histone H1 by P-TEFb is a necessary step in skeletal muscle differentiation
✍ Scribed by Siobhan K. O'Brien; Kendall L. Knight; Tariq M. Rana
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 995 KB
- Volume
- 227
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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.