An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from humans, flies and worms, we found that exons show increased nucleosome-occupancy levels with respect to introns, a finding that we link to differential GC content and nucleosome-disfavoring elements between exons and introns. Analysis of genome-wide chromatin immunoprecipitation data in humans and mice revealed four specific post-translational histone modifications enriched in exons. Our findings indicate that previously described enrichment of H3K36me3 modifications in exons reflects a more fundamental phenomenon, namely increased nucleosome occupancy along exons. Our results suggest an RNA polymerase II-mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure.
Bibliographical noteFunding Information:
We thank D. Schones (Laboratory of Molecular Immunology, US National Heart, Lung and Blood Institute) and Y. Field (Weizmann Institute of Science) for sharing data sets, E. Segal (Weizmann Institute of Science) and M. Kupiec (Tel Aviv University) for critical review of the manuscript, and B. Zornberg for inspiration. S.S. is a fellow of the Edmond J. Safra bioinformatic program at Tel Aviv University. G.A. is supported by a grant from the Israel Science Foundation (ISF 61/09), Joint Germany-Israeli Research Program (ca-139), Deutsche-Israel Project (DIP MI-1317), and European Alternative Splicing Network (EURASNET). E.M. is supported by the Israel Science Foundation (ISF 215/07), the European Union (IRG-206872) and an Alon fellowship. This work was performed in partial fulfillment of the requirements for a Ph.D. degree of S.S., Sackler Faculty of Medicine, Tel Aviv University.