Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells (original) (raw)

Nature Genetics volume 41, pages 246–250 (2009)Cite this article

Abstract

Higher eukaryotes must adapt a totipotent genome to specialized cell types with stable but limited functions. One potential mechanism for lineage restriction is changes in chromatin, and differentiation-related chromatin changes have been observed for individual genes1,2. We have taken a genome-wide view of histone H3 lysine 9 dimethylation (H3K9Me2) and find that differentiated tissues show surprisingly large K9-modified regions (up to 4.9 Mb). These regions are highly conserved between human and mouse and are differentiation specific, covering only ∼4% of the genome in undifferentiated mouse embryonic stem (ES) cells, compared to 31% in differentiated ES cells, ∼46% in liver and ∼10% in brain. These modifications require histone methyltransferase G9a and are inversely related to expression of genes within the regions. We term these regions large organized chromatin K9 modifications (LOCKs). LOCKs are substantially lost in cancer cell lines, and they may provide a cell type–heritable mechanism for phenotypic plasticity in development and disease.

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Acknowledgements

We thank S. Taverna, K. Reddy, R. Ohlsson and C. Sapienza for helpful discussions, and S. Taverna and W. Timp for assistance with illustration. This work was supported by US National Institutes of Health grant P50HG003233 to A.P.F.

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Authors and Affiliations

  1. Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA
    Bo Wen, Hao Wu, Rafael A Irizarry & Andrew P Feinberg
  2. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA
    Bo Wen & Andrew P Feinberg
  3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA
    Hao Wu & Rafael A Irizarry
  4. Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto, 606, Japan
    Yoichi Shinkai

Authors

  1. Bo Wen
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  2. Hao Wu
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  3. Yoichi Shinkai
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  4. Rafael A Irizarry
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  5. Andrew P Feinberg
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Contributions

B.W. and A.P.F. conceived the project. B.W. performed the experiments. H.W. analyzed the data with the guidance of R.A.I. Y.S. provided the mouse G9a knockout and control ES cell lines. A.P.F. supervised the experiments and wrote the paper with B.W.

Corresponding author

Correspondence toAndrew P Feinberg.

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Wen, B., Wu, H., Shinkai, Y. et al. Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells.Nat Genet 41, 246–250 (2009). https://doi.org/10.1038/ng.297

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