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Reciprocal intronic and exonic histone modification regions in humans

Nature Structural & Molecular Biology volume 17, pages 1495–1499 (2010)Cite this article

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Abstract

While much attention has been focused on chromatin at promoters and exons, human genes are mostly composed of intronic sequences. Analyzing published surveys of nucleosomes and 41 chromatin marks in humans, we identified histone modifications specifically associated with 5′ intronic sequences, distinguishable from promoter marks and bulk nucleosomes. These intronic marks were spatially reciprocal to trimethylated histone H3 Lys36 (H3K36me3), typically transitioning near internal exons. Several marks transitioned near bona fide exons, but not near nucleosomes at exon-like sequences. Therefore, we examined whether splicing affects histone marking. Even with considerable changes in regulated alternative splicing, histone marks were stable. Notably, these findings are consistent with exon definition influencing histone marks. In summary, we show that the location of many intragenic marks in humans can be distilled into a simple organizing principle: association with 5′ intronic or 3′ exonic regions.

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Figure 1: Groups of histone marks revealed by PCA.
Figure 2: Intragenic histone modification regions reflect gene architecture.
Figure 3: Histone modification profiles at the alternatively spliced exon of YPEL5 are similar between caffeine-treated SW620 cells expressing different YPEL5 mRNA isoforms.
Figure 4: Histone modification profiles at the alternatively spliced exons of CD45 are similar between B-cell lines stably expressing different CD45 mRNA isoforms.

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Acknowledgements

We thank the following for kindly providing reagents and data: S. Oberdoerffer and A. Rao (Harvard Medical School) for B-cell lines, N. Spies and C. Burge (MIT) for ECR locations, and E. Shema and M. Oren (Weizmann Institute of Science) for H2Bub ChIP-seq data. We also thank H. Madhani and J. Steitz for critical reading of the manuscript and the Guthrie, Yamamoto and Panning groups for helpful discussions. J.T.H. and A.M.P. were supported by individual ARCS Foundation Scholarships. Research support was provided by US National Institutes of Health grants GM21119 to C.G. and CA020535 to K.R.Y. C.G. is an American Cancer Society Research Professor of Molecular Genetics, and K.R.Y. is a consultant with Merck & Co.

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  1. Jason T Huff and Alex M Plocik: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA

    Jason T Huff & Keith R Yamamoto

  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California, USA

    Alex M Plocik & Christine Guthrie

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  1. Jason T Huff
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  2. Alex M Plocik
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Contributions

J.T.H. and A.M.P. designed and performed the analyses and experiments. J.T.H., A.M.P., C.G. and K.R.Y. wrote the manuscript.

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Correspondence to Christine Guthrie or Keith R Yamamoto.

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Supplementary Figs. 1-7 and Supplementary Table 1 (PDF 5571 kb)

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Huff, J., Plocik, A., Guthrie, C. et al. Reciprocal intronic and exonic histone modification regions in humans. Nat Struct Mol Biol 17, 1495–1499 (2010). https://doi.org/10.1038/nsmb.1924

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