Histones comprise the major protein component of chromatin, the scaffold in which the eukaryotic genome is packaged, and are subject to many types of post-translational modifications (PTMs), especially on their flexible tails. These modifications may constitute a 'histone code' and could be used to manage epigenetic information that helps extend the genetic message beyond DNA sequences. This proposed code, read in part by histone PTM–binding 'effector' modules and their associated complexes, is predicted to define unique functional states of chromatin and/or regulate various chromatin-templated processes. A wealth of structural and functional data show how chromatin effector modules target their cognate covalent histone modifications. Here we summarize key features in molecular recognition of histone PTMs by a diverse family of 'reader pockets', highlighting specific readout mechanisms for individual marks, common themes and insights into the downstream functional consequences of the interactions. Changes in these interactions may have far-reaching implications for human biology and disease, notably cancer.
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We apologize to all of the researchers whose important contributions could not be acknowledged because of space constraints. We thank members of the Patel and Allis laboratories as well as the anonymous reviewers for critically reading the manuscript, and A. VanDemark (University of Pittsburgh) and C.P. Hill (University of Utah) for providing coordinates for Rsc4p in Figure 2e. D.J.P. is supported by funds from the Abby Rockefeller Mauze Trust and the Dewitt Wallace and Maloris Foundations, C.D.A. and S.D.T are supported by US National Institutes of Health grants GM53512 and GM63959 and by funds from The Rockefeller University, and A.J.R. is supported by a postdoctoral fellowship from the Irvington Foundation.
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Taverna, S., Li, H., Ruthenburg, A. et al. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nat Struct Mol Biol 14, 1025–1040 (2007). https://doi.org/10.1038/nsmb1338
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