Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn

During mouse embryogenesis, expression of the long non-coding RNA (lncRNA) Airn leads to gene repression and recruitment of Polycomb repressive complexes (PRCs) to varying extents over a 15-Mb domain. The mechanisms remain unclear. Using high-resolution approaches, we show in mouse trophoblast stem cells that Airn expression induces long-range changes to chromatin architecture that coincide with PRC-directed modifications and center around CpG island promoters that contact the Airn locus even in the absence of Airn expression. Intensity of contact between the Airn lncRNA and chromatin correlated with underlying intensity of PRC recruitment and PRC-directed modifications. Deletion of CpG islands that contact the Airn locus altered long-distance repression and PRC activity in a manner that correlated with changes in chromatin architecture. Our data imply that the extent to which Airn expression recruits PRCs to chromatin is controlled by DNA regulatory elements that modulate proximity of the Airn lncRNA product to its target DNA. [Display omitted] •Airn-induced architecture changes coincide with PRC-directed chromatin modifications•Changes center around regions that form prior contacts with Airn locus•Airn lncRNA, PRCs, and PRC-directed modifications are linked by proximity•Specific DNA regulatory elements can modulate repression by Airn in different ways Braceros et al. map interactions between DNA regulatory elements, Polycomb repressive complexes (PRCs), and the lncRNA Airn. They find that the presence of Airn lncRNA and PRCs correlates in lock-step on chromatin and that specific DNA regulatory elements modulate intensity of repression by Airn in different ways.