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Differential chromatin marking of introns and expressed exons by H3K36me3

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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References

  1. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

    CAS  Article  Google Scholar 

  2. The C. elegans sequencing consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018 (1998).

  3. Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811 (1998).

    CAS  Article  Google Scholar 

  4. Timmons, L. & Fire, A. Specific interference by ingested dsRNA. Nature 395, 854 (1998).

    CAS  Article  Google Scholar 

  5. Cui, M. & Han, M. Roles of chromatin factors in C. elegans development. WormBook doi/10.1895/wormbook.1.139.1 (2007).

  6. Ercan, S. et al. X chromosome repression by localization of the C. elegans dosage compensation machinery to sites of transcription initiation. Nat. Genet. 39, 403–408 (2007).

    CAS  Article  Google Scholar 

  7. Whittle, C.M. et al. The genomic distribution and function of histone variant HTZ-1 during C. elegans embryogenesis. PLoS Genet. 4, e1000187 (2008).

    Article  Google Scholar 

  8. Bargmann, C.I. Chemosensation in C. elegans. WormBook doi/10.1895/wormbook.1.123.1 (2006).

  9. Schneider, R. et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat. Cell Biol. 6, 73–77 (2004).

    CAS  Article  Google Scholar 

  10. Bernstein, B.E. et al. Genomic maps and comparative analysis of histone modifications in human and mouse. Cell 120, 169–181 (2005).

    CAS  Article  Google Scholar 

  11. Ng, H.H., Robert, F., Young, R.A. & Struhl, K. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11, 709–719 (2003).

    CAS  Article  Google Scholar 

  12. Pokholok, D.K. et al. Genome-wide map of nucleosome acetylation and methylation in yeast. Cell 122, 517–527 (2005).

    CAS  Article  Google Scholar 

  13. Blumenthal, T. Trans-splicing and operons. WormBook doi/10.1895/wormbook.1.5.1 (2005).

  14. Peters, A.H. et al. Partitioning and plasticity of repressive histone methylation states in mammalian chromatin. Mol. Cell 12, 1577–1589 (2003).

    CAS  Article  Google Scholar 

  15. Martens, J.H. et al. The profile of repeat-associated histone lysine methylation states in the mouse epigenome. EMBO J. 24, 800–812 (2005).

    CAS  Article  Google Scholar 

  16. Brinkman, A.B. et al. Histone modification patterns associated with the human X chromosome. EMBO Rep. 7, 628–634 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Vakoc, C.R., Mandat, S.A., Olenchock, B.A. & Blobel, G.A. Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin. Mol. Cell 19, 381–391 (2005).

    CAS  Article  Google Scholar 

  18. Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007).

    CAS  Article  Google Scholar 

  19. Mikkelsen, T.S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553–560 (2007).

    CAS  Article  Google Scholar 

  20. Krogan, N.J. et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol. Cell. Biol. 23, 4207–4218 (2003).

    CAS  Article  Google Scholar 

  21. Li, J., Moazed, D. & Gygi, S.P. Association of the histone methyltransferase Set2 with RNA polymerase II plays a role in transcription elongation. J. Biol. Chem. 277, 49383–49388 (2002).

    CAS  Article  Google Scholar 

  22. Schaft, D. et al. The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation. Nucleic Acids Res. 31, 2475–2482 (2003).

    CAS  Article  Google Scholar 

  23. Carrozza, M.J. et al. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell 123, 581–592 (2005).

    CAS  Article  Google Scholar 

  24. Keogh, M.C. et al. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123, 593–605 (2005).

    CAS  Article  Google Scholar 

  25. Allemand, E., Batsche, E. & Muchardt, C. Splicing, transcription, and chromatin: a menage a trois. Curr. Opin. Genet. Dev. 18, 145–151 (2008).

    CAS  Article  Google Scholar 

  26. Sims, R.J. III et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol. Cell 28, 665–676 (2007).

    CAS  Article  Google Scholar 

  27. de la Mata, M. et al. A slow RNA polymerase II affects alternative splicing in vivo. Mol. Cell 12, 525–532 (2003).

    CAS  Article  Google Scholar 

  28. Howe, K.J., Kane, C.M. & Ares, M. Jr. Perturbation of transcription elongation influences the fidelity of internal exon inclusion in Saccharomyces cerevisiae. RNA 9, 993–1006 (2003).

    CAS  Article  Google Scholar 

  29. Ren, B. et al. Genome-wide location and function of DNA binding proteins. Science 290, 2306–2309 (2000).

    CAS  Article  Google Scholar 

  30. Song, J.S. et al. Model-based analysis of two-color arrays (MA2C). Genome Biol. 8, R178 (2007).

    Article  Google Scholar 

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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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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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