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Control of Neuronal Gene Transcription and Behavior by the Epigenetic Suppressor Complex G9a/GLP

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Epigenetics, Brain and Behavior

Part of the book series: Research and Perspectives in Neurosciences ((NEUROSCIENCE))

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Abstract

Epigenetic control of cellular phenotypes is governed by numerous enzymes that contribute to post-synthetic modifications of DNA and associated histone proteins. These modifications facilitate the assembly of protein complexes that regulate gene expression in a highly orchestrated fashion. The importance of epigenetic regulators in brain development and function is supported by the strong association between mental retardation in humans and the aberrant structure or expression of various epigenetic regulators

Using conditional mutagenesis in mice, we found that the histone methyltransferase complex G9a/GLP (Ehmt1/Ehmt2 in humans), which controls gene expression via di-methylation of histone 3 on lysine 9 (H3K9me2), regulates cognition and complex behavior in mice. Postnatal neuron-specific loss of G9a/GLP in mice recapitulates key symptoms of a severe mental retardation syndrome in humans that is associated with the reduced expression of GLP/Ehmt1. In an attempt to unravel the mechanism of G9a/GLP regulated cognition and behavior, we will discuss the nature of gene expression changes associated with the loss of G9a/GLP.

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Acknowledgments

I would like to thank Paul Greengard and Alexander Tarakhovsky for their support and discussions and Shrihari Sampath, Myriam Heiman, James Surmeier, and Nathaniel Heintz for their contribution to the work. The work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the National Institute on Drug Abuse (NIDA).

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

    Anne Schaefer

  2. Laboratory of Brain Epigenetics, Friedman Brain Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, 10029, New York, NY, USA

    Anne Schaefer

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  1. Anne Schaefer
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Correspondence to Anne Schaefer .

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Editors and Affiliations

  1. School of Medicine, Center for Metabolism and Epigenetics, University of California at Irvine, Sprague Hall 324, Irvine, 92697, California, USA

    Paolo Sassone Corsi

  2. Recherche Therapeutique, Fondation IPSEN pour la, quai George Gorse 65, Boulogne Billancourt Cedex, 92650, France

    Yves Christen

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Schaefer, A. (2012). Control of Neuronal Gene Transcription and Behavior by the Epigenetic Suppressor Complex G9a/GLP. In: Sassone Corsi, P., Christen, Y. (eds) Epigenetics, Brain and Behavior. Research and Perspectives in Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27913-3_6

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