title: Pre-mRNA splicing is a determinant of histone H3K36 methylation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, University of Colorado Health Sciences Center, Aurora, CO 80045, USA.
authors.forename: Soojin
authors.initials: S
authors.lastname: Kim
authors.forename: Hyunmin
authors.initials: H
authors.lastname: Kim
authors.forename: Nova
authors.initials: N
authors.lastname: Fong
authors.forename: Benjamin
authors.initials: B
authors.lastname: Erickson
authors.forename: David L
authors.initials: DL
authors.lastname: Bentley
mesh_terms: D002460:Cell Line; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D009154:Mutation; D011499:Protein Processing, Post-Translational; D012322:RNA Precursors / Q000378:metabolism*; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger; D017411:Ribonucleoproteins, Small Nuclear; D055544:beta-Globins / Q000235:genetics
chemical_list: D006657:Histones; D012322:RNA Precursors; D022821:RNA Splice Sites; D012333:RNA, Messenger; D017411:Ribonucleoproteins, Small Nuclear; D055544:beta-Globins