A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ 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 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.
Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands.
Maartje C
MC
Brink
Diewertje G E
DG
Piebes
Marloes L
ML
de Groote
Martijn S
MS
Luijsterburg
Corella S
CS
Casas-Delucchi
Roel
R
van Driel
Marianne G
MG
Rots
M Cristina
MC
Cardoso
Pernette J
PJ
Verschure
D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D017930:Genes, Reporter; D016678:Genome / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D014158:Transcription, Genetic
C000715593:CBX1 protein, human; C000715594:CBX5 protein, human; C453799:Cbx3 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D051783:Methyl-CpG-Binding Protein 2; C485184:enhanced green fluorescent protein; D000090266:Chromobox Protein Homolog 5; D049452:Green Fluorescent Proteins