Journal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume 18, Issue 3, Pages 337-U127Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1995
Keywords
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Funding
- Region Ile-de-France
- L'Association pour la Recherche sur le Cancer
- Agence National de la Recherche
- Canceropole Ile-de-France
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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 HP1 gamma, 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 HP1 gamma 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 HP1 gamma as a possible bridging molecule between the chromatin and the maturating mRNA, with a general impact on splicing decisions.
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