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H3.3/H2A.Z double variant–containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions

Nature Genetics volume 41, pages 941–945 (2009)Cite this article

Abstract

To understand how chromatin structure is organized by different histone variants, we have measured the genome-wide distribution of nucleosome core particles (NCPs) containing the histone variants H3.3 and H2A.Z in human cells. We find that a special class of NCPs containing both variants is enriched at 'nucleosome-free regions' of active promoters, enhancers and insulator regions. We show that preparative methods used previously in studying nucleosome structure result in the loss of these unstable double-variant NCPs. It seems likely that this instability facilitates the access of transcription factors to promoters and other regulatory sites in vivo. Other combinations of variants have different distributions, consistent with distinct roles for histone variants in the modulation of gene expression.

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Figure 1: H3.3/H2A.Z NCPs mark 'nucleosome-free regions' of active promoters.
Figure 2: H3.3/H2A.Z NCPs enriched at other regulatory elements.
Figure 3: Histone variants near transcription termination sites (TTSs).
Figure 4: Different combinations of histone variants have distinctive distribution patterns across genes.
Figure 5: Schematic representation of the dynamic exchange of factors at a transcriptionally active TSS or other regulatory elements.

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Acknowledgements

We thank H. Tagami, Y. Nakatani and G. Almouzni for H3.3-Flag cells, T. Roh, D.E. Schones and P. Khil for Solexa pipeline analysis and S. Sharmeen and G. Poy for Solexa sequencing. We also acknowledge members of the Felsenfeld laboratory for criticism of the manuscript. This research was supported by the Intramural Research Programs of the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.

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Author notes

  1. Chunyuan Jin and Chongzhi Zang: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

    Chunyuan Jin & Gary Felsenfeld

  2. Department of Physics, The George Washington University, Washington, DC, USA

    Chongzhi Zang & Weiqun Peng

  3. Laboratory of Molecular Immunology, The National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

    Gang Wei, Kairong Cui & Keji Zhao

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  1. Chunyuan Jin
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  2. Chongzhi Zang
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  3. Gang Wei
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  5. Weiqun Peng
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  6. Keji Zhao
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  7. Gary Felsenfeld
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Contributions

C.J. and G.F. designed the experiments and C.J. carried them out, C.Z. and W.P. performed computational analyses, G.W. did template preparation for Solexa sequencing, K.C. contributed to the study, C.J., C.Z., W.P., K.Z. and G.F. analyzed the data, C.J., C.Z., W.P. and G.F. wrote the paper, and K.Z. and G.F. directed the study.

Corresponding authors

Correspondence to Keji Zhao or Gary Felsenfeld.

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Supplementary Note, Supplementary Figures 1–13 and Supplementary Table 1 (PDF 839 kb)

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Jin, C., Zang, C., Wei, G. et al. H3.3/H2A.Z double variant–containing nucleosomes mark 'nucleosome-free regions' of active promoters and other regulatory regions. Nat Genet 41, 941–945 (2009). https://doi.org/10.1038/ng.409

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