UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing

Pradeepa, MM; Sutherland, HG; Ule, J; Grimes, GR; Bickmore, WA; (2012) Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing. PLoS Genetics , 8 (5) , Article e1002717. 10.1371/journal.pgen.1002717. Green open access

[thumbnail of 1392064.pdf]
Preview
PDF
1392064.pdf

Download (1MB)

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.

Type: Article
Title: Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pgen.1002717
Publisher version: http://dx.doi.org/10.1371/journal.pgen.1002717
Language: English
Additional information: © 2012 Pradeepa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: 3T3 Cells Adaptor Proteins, Signal Transducing/*genetics/metabolism Alternative Splicing/*genetics Animals Chromatin/genetics/metabolism Fibroblasts/cytology Gene Expression Regulation *Histones/genetics/metabolism Methylation Mice Nuclear Proteins/genetics/metabolism *Protein Isoforms/genetics/metabolism Protein Structure, Tertiary RNA-Binding Proteins/genetics/metabolism Transcription Factors/*genetics/metabolism
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1392064
Downloads since deposit
148Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item