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The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression

Nature Structural & Molecular Biology volume 14, pages 1070–1076 (2007)Cite this article

Abstract

Although it is believed that the interconversion between permissive and refractory chromatin structures is important in regulating gene transcription, this process is poorly understood. Central to addressing this issue is to elucidate how a nucleosomal array folds into higher-order chromatin structures. Such findings can then provide new insights into how the folding process is regulated to yield different functional states. Using well-defined in vitro chromatin-assembly and transcription systems, we show that a small acidic region on the surface of the nucleosome is crucial both for the folding of a nucleosomal template into the 30-nm chromatin fiber and for the efficient repression of transcription, thereby providing a mechanistic link between these two essential processes. This structure-function relationship has been exploited by complex eukaryotic cells through the replacement of H2A with the specific variant H2A.Bbd, which naturally lacks an acidic patch.

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Figure 1: The acidic patch facilitates intranucleosomal interactions.
Figure 2: The partially neutralized acidic patch of H2A.Bbd inhibits the chromatin fiber folding pathway.
Figure 3: The acidic patch inhibits the formation of condensed tertiary chromatin structures.
Figure 4: Efficient transcriptional repression of a chromatin template requires the acidic patch.

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Acknowledgements

We especially thank K. Luger (Colorado State University, Fort Collins) for providing recombinant histones and sharing unpublished data and for many helpful discussions, Y. Bao (Colorado State University, Fort Collins) for recombinant H2A.Bbd, J. Hansen (Colorado State University, Fort Collins) for continued support and critical reading of this manuscript, and T. Soboleva (The John Curtin School of Medical Research) for analysis of published gene expression array data. We also thank D. Rhodes (Medical Research Council Laboratory of Molecular Biology) for the 601-200-12 DNA template and J. Workman (Stowers Institute for Medical Research) for the HIV-208-5S DNA template. This work was supported by an Australian Research grant to J.Y.F. and D.J.T.

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Author notes

  1. Jiansheng Zhou and Jun Y Fan: These authors contributed equally to this work.

Authors and Affiliations

  1. The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, 2601, Australian Capital Territory, Australia

    Jiansheng Zhou, Jun Y Fan, Danny Rangasamy & David J Tremethick

Authors
  1. Jiansheng Zhou
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  2. Jun Y Fan
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  4. David J Tremethick
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Contributions

J.Z. and J.Y.F. carried out the research, D.R. generated mutant histone clones, and D.J.T. devised the project and wrote the paper.

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Correspondence to David J Tremethick.

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Supplementary Figures 1–4, Supplementary Table 1 (PDF 1063 kb)

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Zhou, J., Fan, J., Rangasamy, D. et al. The nucleosome surface regulates chromatin compaction and couples it with transcriptional repression. Nat Struct Mol Biol 14, 1070–1076 (2007). https://doi.org/10.1038/nsmb1323

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