Proximity-dependent recruitment of Polycomb repressive complexes by the lncRNA Airn
Aki K. Braceros,
Megan D. Schertzer,
Arina Omer,
Jackson B. Trotman,
Eric S. Davis,
Jill M. Dowen,
Douglas H. Phanstiel,
Erez Lieberman Aiden,
J. Mauro Calabrese
Affiliations
Aki K. Braceros
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Mechanistic, Interdisciplinary Studies of Biological Systems, University of North Carolina, Chapel Hill, NC 27599, USA
Megan D. Schertzer
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA
Arina Omer
Center for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
Jackson B. Trotman
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
Eric S. Davis
Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA
Jill M. Dowen
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA
Douglas H. Phanstiel
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC 27599, USA; Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC 27599, USA
Erez Lieberman Aiden
Center for Genome Architecture, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
J. Mauro Calabrese
Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA; Corresponding author
Summary: 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.
