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Nucleosome positioning as a determinant of exon recognition

Nature Structural & Molecular Biology volume 16, pages 996–1001 (2009)Cite this article

Abstract

Chromatin structure influences transcription, but its role in subsequent RNA processing is unclear. Here we present analyses of high-throughput data that imply a relationship between nucleosome positioning and exon definition. First, we have found stable nucleosome occupancy within human and Caenorhabditis elegans exons that is stronger in exons with weak splice sites. Conversely, we have found that pseudoexons—intronic sequences that are not included in mRNAs but are flanked by strong splice sites—show nucleosome depletion. Second, the ratio between nucleosome occupancy within and upstream from the exons correlates with exon-inclusion levels. Third, nucleosomes are positioned central to exons rather than proximal to splice sites. These exonic nucleosomal patterns are also observed in non-expressed genes, suggesting that nucleosome marking of exons exists in the absence of transcription. Our analysis provides a framework that contributes to the understanding of splicing on the basis of chromatin architecture.

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Figure 1: Observed and predicted nucleosome occupancy.
Figure 2: Nuclesome occupancy and expression of genes and exons.
Figure 3: Nucleosome occupancy in internal exons of different lengths, initial exons and terminal exons.
Figure 4: Profile of histone modifications in expressed genes in resting CD4+ T cells.

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Acknowledgements

We thank D.E. Schones for help with the data and its interpretation and members of the Guigó laboratory, especially D. Gonzalez, for help with data analysis. This work was supported by the Spanish Ministry of Science with fellowships to M.S. and S.A., and with grant number BIO2006-03380 to R.G.

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Author notes

  1. Hagen Tilgner and Christoforos Nikolaou: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain

    Hagen Tilgner, Christoforos Nikolaou, Sonja Althammer, Michael Sammeth, Miguel Beato, Juan Valcárcel & Roderic Guigó

  2. Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain

    Juan Valcárcel

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Correspondence to Roderic Guigó.

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Tilgner, H., Nikolaou, C., Althammer, S. et al. Nucleosome positioning as a determinant of exon recognition. Nat Struct Mol Biol 16, 996–1001 (2009). https://doi.org/10.1038/nsmb.1658

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