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The specific role of histone deacetylase 2 in adult neurogenesis

Published online by Cambridge University Press:  14 April 2010

Melanie Jawerka ,
Dilek Colak ,
Leda Dimou ,
Carmen Spiller ,
Sabine Lagger ,
Rusty L. Montgomery ,
Eric N. Olson ,
Wolfgang Wurst ,
Martin Göttlicher  and
Magdalena Götz
Melanie Jawerka
Affiliation:
Institute for Stem Cell Research, HelmholtzZentrum Munich, German Research Center for Environmental Health, Neuherberg/Munich, Germany
Dilek Colak
Affiliation:
Institute for Stem Cell Research, HelmholtzZentrum Munich, German Research Center for Environmental Health, Neuherberg/Munich, Germany
Leda Dimou
Affiliation:
Department of Physiological Genomics, Institute of Physiology, University of Munich, Munich, Germany
Carmen Spiller
Affiliation:
Institute for Toxicology, HelmholtzZentrum Munich German Research Center for Environmental Health, Neuherberg/Munich, Germany
Sabine Lagger
Affiliation:
Max F. Perutz Laboratories, Medical University of Vienna, Institute of Medical Biochemistry, Vienna, Austria
Rusty L. Montgomery
Affiliation:
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, TX, USA
Eric N. Olson
Affiliation:
Department of Molecular Biology, The University of Texas Southwestern Medical Center at Dallas, TX, USA
Wolfgang Wurst
Affiliation:
Institute for Developmental Genetics, HelmholtzZentrum Munich, German Research Center for Environmental Health, Neuherberg/Munich, Germany MPI for Psychiatry, Munich, Germany
Martin Göttlicher
Affiliation:
Institute for Toxicology, HelmholtzZentrum Munich German Research Center for Environmental Health, Neuherberg/Munich, Germany Institute of Toxicology and Environmental Hygiene Technical University Munich, Germany
Magdalena Götz*
Affiliation:
Institute for Stem Cell Research, HelmholtzZentrum Munich, German Research Center for Environmental Health, Neuherberg/Munich, Germany Department of Physiological Genomics, Institute of Physiology, University of Munich, Munich, Germany
*
Correspondence should be addressed to: Magdalena Götz, Institute for Stem Cell Research HelmholtzZentrum München, Neuherberg/Munich, Germany phone: +49-89-31873750 fax: +49-89-31873761 email: magdalena.goetz@helmholtz-muenchen.de
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Abstract

Gene expression changes during cell differentiation are thought to be coordinated by histone modifications, but still little is known about the role of specific histone deacetylases (HDACs) in cell fate decisions in vivo. Here we demonstrate that the catalytic function of HDAC2 is required in adult, but not embryonic neurogenesis. While brain development and adult stem cell fate were normal upon conditional deletion of HDAC2 or in mice lacking the catalytic activity of HDAC2, neurons derived from both zones of adult neurogenesis die at a specific maturation stage. This phenotype is correlated with an increase in proliferation and the aberrant maintenance of proteins normally expressed only in progenitors, such as Sox2, also into some differentiating neurons, suggesting that HDAC2 is critically required to silence progenitor transcripts during neuronal differentiation of adult generated neurons. This cell-autonomous function of HDAC2 exclusively in adult neurogenesis reveals clear differences in the molecular mechanisms regulating neurogenesis during development and in adulthood.

Keywords

Neural fateneural stem cellsneuronal differentiationepigeneticshistone modification
Type
Research Article
Information
Neuron Glia Biology , Volume 6 , Issue 2 , May 2010 , pp. 93 - 107
Copyright
Copyright © Cambridge University Press 2010

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