A Role for MeCP2 in Switching Gene Activity via Chromatin Unfolding and HP1c Displacement

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 HP1c at the chromosomal domain and an increased HP1c mobility, which is not observed for HP1a and HP1b. 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. Citation: Brink MC, Piebes DGE, de Groote ML, Luijsterburg MS, Casas-Delucchi CS, et al. (2013) A Role for MeCP2 in Switching Gene Activity via Chromatin Unfolding and HP1c Displacement. PLoS ONE 8(7): e69347. doi:10.1371/journal.pone.0069347 Editor: Nicoletta Landsberger, University of Insubria, Italy Received February 8, 2013; Accepted June 7, 2013; Published July 2 , 2013 Copyright: 2013 Brink et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Support was provided by the Netherlands Organization for Scientific Research VIDI-016041311, NWO-Meervoud-83607001 to PJV, VIDI-91786373 to MGR and Deutsche Forschungsgemeinschaft to MCC. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interest exist. * E-mail: [email protected] . These authors contributed equally to this work. ¤ Current address: Department of Toxicogenetics, Leiden University Medical Center, Leiden, the Netherlands