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.

journal_name

Nat Struct Mol Biol

authors

Saint-André V,Batsché E,Rachez C,Muchardt C

doi

10.1038/nsmb.1995

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

337-44

issue

3

eissn

1545-9993

issn

1545-9985

pii

nsmb.1995

journal_volume

18

pub_type

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