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KAP1-Mediated Epigenetic Repression in the Forebrain Modulates Behavioral Vulnerability to Stress

Jakobsson, Johan LU ; Cordero, Maria Isabel ; Bisaz, Reto; Groner, Anna C.; Busskamp, Volker; Bensadoun, Jean-Charles; Cammas, Florence; Losson, Régine; Mansuy, Isabelle M. and Sandi, Carmen , et al. (2008) In Neuron 60(5). p.818-831
Abstract
KAP1 is an essential cofactor of KRAB-zinc finger proteins, a family of vertebrate-specific epigenetic repressors of largely unknown functions encoded in the hundreds by the mouse and human genomes. Here, we report that KAP1 is expressed at high levels and necessary for KRAB-mediated repression in mature neurons of the mouse brain. Mice deleted for KAP1 in the adult forebrain exhibit heightened levels of anxiety-like and exploratory activity and stress-induced alterations in spatial learning and memory. In the hippocampus, a small number of genes are dysregulated, including some imprinted genes. Chromatin analyses of the promoters of two genes markedly upregulated in knockout mice reveal decreased histone 3 K9-trimethylation and increased... (More)
KAP1 is an essential cofactor of KRAB-zinc finger proteins, a family of vertebrate-specific epigenetic repressors of largely unknown functions encoded in the hundreds by the mouse and human genomes. Here, we report that KAP1 is expressed at high levels and necessary for KRAB-mediated repression in mature neurons of the mouse brain. Mice deleted for KAP1 in the adult forebrain exhibit heightened levels of anxiety-like and exploratory activity and stress-induced alterations in spatial learning and memory. In the hippocampus, a small number of genes are dysregulated, including some imprinted genes. Chromatin analyses of the promoters of two genes markedly upregulated in knockout mice reveal decreased histone 3 K9-trimethylation and increased histone 3 and histone 4 acetylation. We propose a model in which the tethering of KAP1-associated chromatin remodeling factors via KRAB-ZFPs epigenetically controls gene expression in the hippocampus, thereby conditioning responses to behavioral stress. (Less)
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type
Contribution to journal
publication status
published
subject
in
Neuron
volume
60
issue
5
pages
818 - 831
publisher
Cell Press
external identifiers
  • scopus:57049118276
ISSN
0896-6273
DOI
10.1016/j.neuron.2008.09.036
language
English
LU publication?
no
id
23c6a340-75ae-403b-b253-d03e5275c42c
date added to LUP
2016-11-18 12:08:56
date last changed
2017-08-20 05:04:26
@article{23c6a340-75ae-403b-b253-d03e5275c42c,
  abstract     = {KAP1 is an essential cofactor of KRAB-zinc finger proteins, a family of vertebrate-specific epigenetic repressors of largely unknown functions encoded in the hundreds by the mouse and human genomes. Here, we report that KAP1 is expressed at high levels and necessary for KRAB-mediated repression in mature neurons of the mouse brain. Mice deleted for KAP1 in the adult forebrain exhibit heightened levels of anxiety-like and exploratory activity and stress-induced alterations in spatial learning and memory. In the hippocampus, a small number of genes are dysregulated, including some imprinted genes. Chromatin analyses of the promoters of two genes markedly upregulated in knockout mice reveal decreased histone 3 K9-trimethylation and increased histone 3 and histone 4 acetylation. We propose a model in which the tethering of KAP1-associated chromatin remodeling factors via KRAB-ZFPs epigenetically controls gene expression in the hippocampus, thereby conditioning responses to behavioral stress.},
  author       = {Jakobsson, Johan and Cordero, Maria Isabel  and Bisaz, Reto and Groner, Anna C. and Busskamp, Volker and Bensadoun, Jean-Charles and Cammas, Florence and Losson, Régine and Mansuy, Isabelle M.  and Sandi, Carmen  and Trono, Didier},
  issn         = {0896-6273},
  language     = {eng},
  month        = {12},
  number       = {5},
  pages        = {818--831},
  publisher    = {Cell Press},
  series       = {Neuron},
  title        = {KAP1-Mediated Epigenetic Repression in the Forebrain Modulates Behavioral Vulnerability to Stress},
  url          = {http://dx.doi.org/10.1016/j.neuron.2008.09.036},
  volume       = {60},
  year         = {2008},
}