A Role for MeCP2 in Switching Gene Activity via Chromatin Unfolding and HP1 gamma Displacement

作者：Brink Maartje C; Piebes Diewertje G E; de Groote Marloes L; Luijsterburg Martijn S; Casas Delucchi Corella S; van Driel Roel; Rots Marianne G; Cardoso M Cristina; Verschure Pernette J^*

来源：PLos One, 2013, 8(7): e69347.

DOI：10.1371/journal.pone.0069347

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 HP1 gamma at the chromosomal domain and an increased HP1 gamma mobility, which is not observed for HP1 alpha and HP1 beta. 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.

• 出版日期2013-7-23