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Nat Struct Mol Biol. 2011 Mar;18(3):337-44. doi: 10.1038/nsmb.1995. Epub 2011 Feb 27.

Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons.

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Institut Pasteur, Département de Biologie du Développement, Unité de Régulation Epigénétique, Paris, France.


Pre-messenger RNAs (pre-mRNAs) maturation is initiated cotranscriptionally. It is therefore conceivable that chromatin-borne information participates in alternative splicing. Here we find that elevated levels of trimethylation of histone H3 on Lys9 (H3K9me3) are a characteristic of the alternative exons of several genes including CD44. On this gene the chromodomain protein HP1γ, frequently defined as a transcriptional repressor, facilitates inclusion of the alternative exons via a mechanism involving decreased RNA polymerase II elongation rate. In addition, accumulation of HP1γ on the variant region of the CD44 gene stabilizes association of the pre-mRNA with the chromatin. Altogether, our data provide evidence for localized histone modifications impacting alternative splicing. They further implicate HP1γ as a possible bridging molecule between the chromatin and the maturating mRNA, with a general impact on splicing decisions.

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