title: Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing.
abstract: Increasing evidence suggests that chromatin modifications have important roles in modulating constitutive or alternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognize tri-methylated H3K36 and that, like this histone modification, the Psip1 short (p52) isoform is enriched at active genes. We show that the p52, but not the long (p75), isoform of Psip1 co-localizes and interacts with Srsf1 and other proteins involved in mRNA processing. The level of H3K36me3 associated Srsf1 is reduced in Psip1 mutant cells and alternative splicing of specific genes is affected. Moreover, we show altered Srsf1 distribution around the alternatively spliced exons of these genes in Psip1 null cells. We propose that Psip1/p52, through its binding to both chromatin and splicing factors, might act to modulate splicing.
authors.affiliation: MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Madapura M
authors.initials: MM
authors.lastname: Pradeepa
authors.forename: Heidi G
authors.initials: HG
authors.lastname: Sutherland
authors.forename: Jernej
authors.initials: J
authors.lastname: Ule
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Grimes
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C504649:PSIP1 protein, human; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D000068103:Serine-Arginine Splicing Factors