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A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ displacement.

Brink, Maartje C. and Piebes, Diewertje G. E. and de Groote, Marloes L. and Luijsterburg, Martijn S. and Casas-Delucchi, Corella S. and van Driel, Roel and Rots, Marianne G. and Cardoso, M. Cristina and Verschure, Pernette J. (2013):
A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ displacement.
In: PloS one, pp. e69347, 8, (7), ISSN 1932-6203, [Article]

Abstract

Methyl-CpG-binding protein 2 (MeCP2) is generally considered to act as a transcriptional repressor, whereas recent studies suggest that MeCP2 is also involved in transcription activation. To gain insight into this dual function of MeCP2, we assessed the impact of MeCP2 on higher-order chromatin structure in living cells using mammalian cell systems harbouring a lactose operator and reporter gene-containing chromosomal domain to assess the effect of lactose repressor-tagged MeCP2 (and separate MeCP2 domains) binding in living cells. Our data reveal that targeted binding of MeCP2 elicits extensive chromatin unfolding. MeCP2-induced chromatin unfolding is triggered independently of the methyl-cytosine-binding domain. Interestingly, MeCP2 binding triggers the loss of HP1γ at the chromosomal domain and an increased HP1γ mobility, which is not observed for HP1α and HP1β. Surprisingly, MeCP2-induced chromatin unfolding is not associated with transcriptional activation. Our study suggests a novel role for MeCP2 in reorganizing chromatin to facilitate a switch in gene activity.

Item Type: Article
Erschienen: 2013
Creators: Brink, Maartje C. and Piebes, Diewertje G. E. and de Groote, Marloes L. and Luijsterburg, Martijn S. and Casas-Delucchi, Corella S. and van Driel, Roel and Rots, Marianne G. and Cardoso, M. Cristina and Verschure, Pernette J.
Title: A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ displacement.
Language: English
Abstract:

Methyl-CpG-binding protein 2 (MeCP2) is generally considered to act as a transcriptional repressor, whereas recent studies suggest that MeCP2 is also involved in transcription activation. To gain insight into this dual function of MeCP2, we assessed the impact of MeCP2 on higher-order chromatin structure in living cells using mammalian cell systems harbouring a lactose operator and reporter gene-containing chromosomal domain to assess the effect of lactose repressor-tagged MeCP2 (and separate MeCP2 domains) binding in living cells. Our data reveal that targeted binding of MeCP2 elicits extensive chromatin unfolding. MeCP2-induced chromatin unfolding is triggered independently of the methyl-cytosine-binding domain. Interestingly, MeCP2 binding triggers the loss of HP1γ at the chromosomal domain and an increased HP1γ mobility, which is not observed for HP1α and HP1β. Surprisingly, MeCP2-induced chromatin unfolding is not associated with transcriptional activation. Our study suggests a novel role for MeCP2 in reorganizing chromatin to facilitate a switch in gene activity.

Journal or Publication Title: PloS one
Volume: 8
Number: 7
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 12 Nov 2013 13:11
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