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  • Hypothesis
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Binary switches and modification cassettes in histone biology and beyond

Nature volume 425, pages 475–479 (2003)Cite this article

Abstract

An immense number of post-translational modifications on histone proteins have been described and additional sites of modification are still being uncovered. Whereas many direct and indirect connections between certain histone modifications and distinct biological phenomena have now been established, concepts for comprehending the extreme density and variety of these covalent modifications are lacking. Here, we formally introduce localized ‘binary switches’ and ‘modification cassettes’ as new concepts in histone biology, elucidating mechanisms that might govern the biological readout of distinct modification patterns. Specifically, our hypotheses provide missing models for the dynamic readout of stable histone modifications and offer explanations for several long-standing questions embedded in the literature. Our ideas might also apply to non-histone proteins and are open to direct experimental examination.

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Figure 1: Dense clustering of histone marks.
Figure 2: Local binary switches.
Figure 3: Surveillance of putative ‘methyl/phos switches’ in core histones.
Figure 4: Putative ‘cassettes’ and ‘switches’ in histone and non-histone proteins.

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Acknowledgements

We thank all current and past members of the Allis laboratory for their input and support as well as many collaborators with whom we have worked or discussed our ideas. We are especially grateful to T. Jenuwein, D. Reinberg and M. Grunstein for discussions in the process of writing this article. We also thank D. F. Hunt and his laboratory as well as C. M. Barber for their groundbreaking work on the in vivo modification patterns of histones that spurred many of the ideas presented here. W.F. is a Robert Black fellow of the Damon Runyon Cancer Research Foundation. Work in the laboratory of C.D.A. is supported by several grants from the NIH.

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  1. Laboratory of Chromatin Biology, The Rockefeller University, New York, New York, 10021, USA

    Wolfgang Fischle, Yanming Wang & C. David Allis

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  1. Wolfgang Fischle
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  2. Yanming Wang
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  3. C. David Allis
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Correspondence to C. David Allis.

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A provisional US patent has been filed on this work at the University of Virginia. All co-authors and Don Hunt are listed as investors.

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Fischle, W., Wang, Y. & David Allis, C. Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475–479 (2003). https://doi.org/10.1038/nature02017

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