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

Abstract : 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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Submitted on : Wednesday, June 17, 2020 - 1:39:54 PM
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Violaine Saint-André, Eric Batsche, Christophe Rachez, Christian Muchardt. Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons. Nature Structural and Molecular Biology, 2011, 18 (3), pp.337-344. ⟨10.1038/nsmb.1995⟩. ⟨pasteur-02871948⟩



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