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An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation

Oncogene volume 20, pages 3007–3013 (2001)Cite this article

Alteration of chromatin is central to genomic regulation. Chromatin is composed of nucleosomes which are particles consisting of DNA in association with an octamer of two molecules each of the core histone proteins (H2A, H2B, H3 and H4) as well as the linker histone H1. Alterations in chromatin structure modulate the expression of underlying genes; transcriptional induction or repression typically requires chromatin remodeling. One type of alteration is covalent modification of the end of histones, and in particular, the amino termini of the core histones, which extend from the nucleosome, and may interact with neighboring nucleosomes (Luger et al., 1997). The last 5 years has witnessed a remarkable expansion of research in this area, owing largely to the contemporaneous discoveries of the first nuclear histone acetyltransferase as a coactivator of transcription (Brownell et al., 1996) and the first histone deacetylase as a corepressor of transcription (Taunton et al., 1996). These discoveries have been followed by investigations into mechanism and effects of acetylation, and significantly, identification of other covalent modifications including phosphorylation, methylation and ubiquitination, as regulators of transcription.

This review focuses on recent studies of histone covalent modifications. The array of such modifications will be discussed and the identity of the enzymes responsible, as this has been revealing of the biological role of the modifications. Summaries of the current knowledge of the modification sites and enzymes responsible are presented (Tables 1 and 2). Recent evidence that acetylation of histones and factors acts positively or negatively in concert with other modifications are discussed. Finally, data investigating the mechanisms of these modifications are reviewed.

Table 1 Histone modifications
Full size table
Table 2 Histone modification enzymes
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Figure 1
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  1. Molecular Genetics Program, Wistar Institute, Philadelphia, 19104, PA, USA

    Shelley L Berger

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Berger, S. An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation. Oncogene 20, 3007–3013 (2001). https://doi.org/10.1038/sj.onc.1204324

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