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Complex Exon-Intron Marking by Histone Modifications Is Not Determined Solely by Nucleosome Distribution

Dhami, P; Saffrey, P; Bruce, AW; Dillon, SC; Chiang, K; Bonhoure, N; Koch, CM; ... Vetrie, D; + view all (2010) Complex Exon-Intron Marking by Histone Modifications Is Not Determined Solely by Nucleosome Distribution. PLOS ONE , 5 (8) , Article e12339. 10.1371/journal.pone.0012339. Green open access

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Abstract

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons ("exon-intron marking"), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing.

Type: Article
Title: Complex Exon-Intron Marking by Histone Modifications Is Not Determined Solely by Nucleosome Distribution
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0012339
Publisher version: http://dx.doi.org/10.1371/journal.pone.0012339
Language: English
Additional information: © 2010 Dhami 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. The Wellcome Trust (http://www.wellcome.ac.uk/); The National Institute for Health Research in England (http://www.nihr.ac.uk/Pages/default.aspx); The National Human Genome Research Institute (http://www.genome.gov/) Grant No: U01HG003168; Ministry of Education, Czech Republic Grant No.6007665801. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: HUMAN GENOME, TRANSCRIPTION ELONGATION, CHROMATIN SIGNATURES, CELL-LINE, IN-VITRO, ELEMENTS, REGIONS, GENES, POLYADENYLATION, METHYLATIONS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
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 Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/133605
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