KAP1-Mediated Epigenetic Repression in the Forebrain Modulates Behavioral Vulnerability to Stress
(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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- author
- publishing date
- 2008-12-10
- 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
- 2022-04-24 19:14:34
@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 = {{https://lup.lub.lu.se/search/files/17102451/KAP1.pdf}}, doi = {{10.1016/j.neuron.2008.09.036}}, volume = {{60}}, year = {{2008}}, }