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Multiple roles of class I HDACs in proliferation, differentiation, and development

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Abstract

Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future.

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Acknowledgments

We wish to thank Camille Du Roure (Phocus, Basel), Benjamin Herquel (IGBMC, Strasbourg), Arnaud Krebs, and Oliver Truee for useful comments and suggestions on the manuscript. This work was supported by the Novartis Research Foundation and the SystemsX RTD Cellplasticity project.

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  1. Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, PO Box 2543, Maulbeerstrasse 66, 4058, Basel, Switzerland

    Nina Reichert, Mohamed-Amin Choukrallah & Patrick Matthias

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  1. Nina Reichert
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  2. Mohamed-Amin Choukrallah
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Correspondence to Patrick Matthias.

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N. Reichert and M.-A. Choukrallah contributed equally to this work.

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Reichert, N., Choukrallah, MA. & Matthias, P. Multiple roles of class I HDACs in proliferation, differentiation, and development. Cell. Mol. Life Sci. 69, 2173–2187 (2012). https://doi.org/10.1007/s00018-012-0921-9

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