Proximity-dependent recruitment of Polycomb Repressive Complexes by the lncRNAAirn

Abstract

ABSTRACTDuring mouse embryogenesis, expression of the lncRNAAirninduces gene silencing and recruits Polycomb Repressive Complexes (PRCs) to varying extents over a 15 megabase domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells thatAirnexpression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact theAirnlocus even in the absence ofAirnexpression. Intensity of contact betweenAirnlncRNA and target chromatin correlated with underlying intensity of PRC-directed chromatin modifications. Deletion of CpG islands that form contacts withAirnaltered long-distance silencing and PRC activity in a manner that correlated with changes in chromatin architecture. We conclude thatAirnis a potentcis-acting lncRNA whose primary functions of transcriptional repression and PRC recruitment are controlled by an equilibratory network of DNA regulatory elements that modulate its frequency of contact with target chromatin.