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Differential chromatin marking of introns and expressed exons by H3K36me3

Nature Genetics volume 41, pages 376–381 (2009)Cite this article

Abstract

Variation in patterns of methylations of histone tails reflects and modulates chromatin structure and function1. To provide a framework for the analysis of chromatin function in Caenorhabditis elegans, we generated a genome-wide map of histone H3 tail methylations. We find that C. elegans genes show distributions of histone modifications that are similar to those of other organisms, with H3K4me3 near transcription start sites, H3K36me3 in the body of genes and H3K9me3 enriched on silent genes. We also observe a novel pattern: exons are preferentially marked with H3K36me3 relative to introns. H3K36me3 exon marking is dependent on transcription and is found at lower levels in alternatively spliced exons, supporting a splicing-related marking mechanism. We further show that the difference in H3K36me3 marking between exons and introns is evolutionarily conserved in human and mouse. We propose that H3K36me3 exon marking in chromatin provides a dynamic link between transcription and splicing.

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Figure 1: Patterns of histone methylations across C. elegans genes.
Figure 2: H3K36me3 is enriched across C. elegans exonic chromatin.
Figure 3: Alternative exons have lower H3K36me3 signal than constitutive exons.
Figure 4: H3K36me3 is enriched across human and mouse exonic chromatin.

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Acknowledgements

We thank all the members of our modENCODE consortium for help and advice, and especially J. Lieb's laboratory for help with ChIP protocol development and S. Strome's laboratory for discussions about H3K36me3. We are very grateful to H. Holster for expert microarray processing at Roche. This work was supported by National Human Genome Research Institute modENCODE grant 1-U01-HG004270-01, by a Wellcome Trust Senior Research Fellowship (054523) and Cambridge Newton Trust funding to J.A., by a Gates Foundation studentship to P.K.-Z. and by a Wellcome Trust Research Career Development Fellowship (083563) to T.D.

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Authors and Affiliations

  1. The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

    Paulina Kolasinska-Zwierz, Thomas Down, Isabel Latorre & Julie Ahringer

  2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, 02115, Massachusetts, USA

    Tao Liu & X Shirley Liu

  3. Department of Biostatistics, Harvard School of Public Health, Boston, 02115, Massachusetts, USA

    X Shirley Liu

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  1. Paulina Kolasinska-Zwierz
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  4. Tao Liu
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  6. Julie Ahringer
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Contributions

J.A. and P.K.-Z. designed the study. P.K.-Z. performed the experiments. P.K.-Z., T.D. and J.A. designed the data analyses. T.D., P.K.-Z., T.L., X.S.L. and J.A. performed the data analyses. I.L. and P.K.-Z. contributed to protocol development. J.A. wrote the paper with help from P.K-Z. and T.D.

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Correspondence to Julie Ahringer.

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Kolasinska-Zwierz, P., Down, T., Latorre, I. et al. Differential chromatin marking of introns and expressed exons by H3K36me3. Nat Genet 41, 376–381 (2009). https://doi.org/10.1038/ng.322

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