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

Casas-Delucchi, Corella S. ; Becker, Annette ; Bolius, Janine J. ; Cardoso, M. Cristina (2012)
Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization.
In: Nucleic acids research, 40 (22)
Artikel, Bibliographie

Kurzbeschreibung (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.

Typ des Eintrags: Artikel
Erschienen: 2012
Autor(en): Casas-Delucchi, Corella S. ; Becker, Annette ; Bolius, Janine J. ; Cardoso, M. Cristina
Art des Eintrags: Bibliographie
Titel: Targeted manipulation of heterochromatin rescues MeCP2 Rett mutants and re-establishes higher order chromatin organization.
Sprache: Englisch
Publikationsjahr: 2012
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Nucleic acids research
Jahrgang/Volume einer Zeitschrift: 40
(Heft-)Nummer: 22
URL / URN: http://nar.oxfordjournals.org/content/early/2012/08/24/nar.g...
Kurzbeschreibung (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.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Cell Biology and Epigenetics
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Hinterlegungsdatum: 03 Sep 2012 13:04
Letzte Änderung: 05 Mär 2013 10:02
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