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Covalent modifications of histones during development and disease pathogenesis

Abstract

Covalent modifications of histones are central to the regulation of chromatin dynamics, and, therefore, many biological processes involving chromatin, such as replication, repair, transcription and genome stability, are regulated by chromatin and its modifications. In this review, we discuss the biochemical, molecular and genetic properties of the enzymatic machinery involved in four different types of histone modification: acetylation, ubiquitination, phosphorylation and methylation. We also discuss how perturbation of the activity of this enzymatic machinery can cause developmental defects and disease.

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Figure 1: Post-translational modifications of human nucleosomal histones.
Figure 2: Schematic representation of the molecular machinery required for proper histone H3 methylation on lysines 4 and 79.

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Acknowledgements

We are thankful to J. Cote for discussions while writing this review. We are grateful for L. Shilatifard's editorial assistance. The work in S.R.B.'s laboratory is supported by the American Heart Association, Scientist Development Grant (0635008N) and the American Cancer Society, Research Scholar Grant (06-52). The research in A.S.'s laboratory is supported by grants from the US National Institutes of Health (2R01CA089455 and 1R01GM069905).

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Bhaumik, S., Smith, E. & Shilatifard, A. Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol 14, 1008–1016 (2007). https://doi.org/10.1038/nsmb1337

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