title: 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.
authors.affiliation: Institut Pasteur, Département de Biologie du Développement, Unité de Régulation Epigénétique, Paris, France.
authors.forename: Violaine
authors.initials: V
authors.lastname: Saint-André
authors.forename: Eric
authors.initials: E
authors.lastname: Batsché
authors.forename: Christophe
authors.initials: C
authors.lastname: Rachez
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
mesh_terms: D017398:Alternative Splicing; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005091:Exons; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D012319:RNA Polymerase II / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism
chemical_list: C518294:CBX3 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D018960:Hyaluronan Receptors; D012322:RNA Precursors; D012319:RNA Polymerase II; D008239:Lysine