Pre-mRNA splicing is a determinant of histone H3K36 methylation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 33; pp. 13564 - 13569
• Main Authors: Kim, Soojin, Kim, Hyunmin, Fong, Nova, Erickson, Benjamin, Bentley, David L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.08.2011; National Acad Sciences
• Subjects: alternative splicing; beta-Globins - genetics; Biological Sciences; Cell Line; Chromatin; Correlation analysis; Exons; Genes; Genetic mutation; Histones; Histones - genetics; Histones - metabolism; Humans; Introns; messenger RNA; Methylation; Mutation; nucleosomes; Protein Processing, Post-Translational; reporter genes; Ribonucleic acid; Ribonucleoproteins, Small Nuclear; RNA; RNA Precursors - metabolism; RNA Splice Sites - genetics; RNA Splicing; RNA, Messenger; Small nuclear ribonucleoproteins; Splicing; transcription (genetics)
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1109475108

A chromatin code appears to mark introns and exons with distinct patterns of nucleosome enrichment and histone methylation. We investigated whether a causal relationship exists between splicing and chromatin modification by asking whether splice-site mutations affect the methylation of histone H3K36. Deletions of the 3′ splice site in intron 2 or in both introns 1 and 2 of an integrated β-globin reporter gene caused a shift in relative distribution of H3K36 trimethylation away from 5′ ends and toward 3′ ends. The effects of splice-site mutations correlated with enhanced retention of a U5 snRNP subunit on transcription complexes downstream of the gene. In contrast, a poly(A) site mutation did not affect H3K36 methylation. Similarly, global inhibition of splicing by spliceostatin A caused a rapid repositioning of H3K36me3 away from 5′ ends in favor of 3′ ends. These results suggest that the cotranscriptional splicing apparatus influences establishment of normal patterns of histone modification.