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Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization.

Casas-Delucchi, Corella S. and Becker, Annette and Bolius, Janine J. and Cardoso, M. Cristina (2012):
Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization.
In: Nucleic acids research, pp. e176, 40, (22), ISSN 1362-4962, [Online-Edition: http://nar.oxfordjournals.org/content/early/2012/08/24/nar.g...],
[Article]

Abstract

Heterochromatic regions represent a significant portion of the mammalian genome and have been implied in several important cellular processes, including cell division and genomic stability. However, its composition and dynamics remain largely unknown. To better understand how heterochromatin functions and how it is organized within the context of the cell nucleus, we have developed molecular tools allowing the targeting of virtually any nuclear factor specifically to heterochromatic regions and, thereby, the manipulation, also in a temporally controlled manner, of its composition. To validate our approach, we have ectopically targeted MeCP2 chromatin binding deficient Rett mutants to constitutive heterochromatic regions and analyze its functional consequences. We could show that, once bound to their endogenous target regions, their ability to re-organize higher order chromatin structure is restored. Furthermore, a temporally controlled targeting strategy allowed us to monitor MeCP2-mediated chromatin rearrangements in vivo and to visualize large-scale chromatin movements over several micrometers, as well as heterochromatic foci fusion events. This novel strategy enables specific tethering of any protein to heterochromatin and lays the ground for controlled manipulation of its composition and organization.

Item Type: Article
Erschienen: 2012
Creators: Casas-Delucchi, Corella S. and Becker, Annette and Bolius, Janine J. and Cardoso, M. Cristina
Title: Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization.
Language: English
Abstract:

Heterochromatic regions represent a significant portion of the mammalian genome and have been implied in several important cellular processes, including cell division and genomic stability. However, its composition and dynamics remain largely unknown. To better understand how heterochromatin functions and how it is organized within the context of the cell nucleus, we have developed molecular tools allowing the targeting of virtually any nuclear factor specifically to heterochromatic regions and, thereby, the manipulation, also in a temporally controlled manner, of its composition. To validate our approach, we have ectopically targeted MeCP2 chromatin binding deficient Rett mutants to constitutive heterochromatic regions and analyze its functional consequences. We could show that, once bound to their endogenous target regions, their ability to re-organize higher order chromatin structure is restored. Furthermore, a temporally controlled targeting strategy allowed us to monitor MeCP2-mediated chromatin rearrangements in vivo and to visualize large-scale chromatin movements over several micrometers, as well as heterochromatic foci fusion events. This novel strategy enables specific tethering of any protein to heterochromatin and lays the ground for controlled manipulation of its composition and organization.

Journal or Publication Title: Nucleic acids research
Volume: 40
Number: 22
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
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Date Deposited: 03 Sep 2012 13:04
Official URL: http://nar.oxfordjournals.org/content/early/2012/08/24/nar.g...
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