Chu, Hsueh-PingFroberg, JohnKesner, BarryOh, Hyun JungJi, FeiSadreyev, RuslanPinter, Stefan F.Lee, Jeannie2018-02-262017Chu, Hsueh-Ping, John E. Froberg, Barry Kesner, Hyun Jung Oh, Fei Ji, Ruslan Sadreyev, Stefan F. Pinter, and Jeannie T. Lee. 2017. “PAR-TERRA directs homologous sex chromosome pairing.” Nature structural & molecular biology 24 (8): 620-631. doi:10.1038/nsmb.3432. http://dx.doi.org/10.1038/nsmb.3432.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34869004In mammals, homologous chromosomes rarely pair outside of meiosis. An exception is the X-chromosome, which transiently pairs during X-chromosome inactivation (XCI). How two chromosomes find each other in 3D space is not known. Here, we reveal a required interaction between the X-inactivation center (Xic) and the telomere in mouse embryonic stem cells. The sub-telomeric, pseudoautosomal region (PAR) of both sex chromosomes (X,Y) also undergoes pairing. PAR transcribes a class of telomeric RNA, dubbed “PAR-TERRA”, which accounts for a vast majority of all TERRA transcripts. PAR-TERRA binds throughout the genome, including PAR and Xic. PAR-TERRA anchors the Xic to PAR, creating a “tetrad” of pairwise homologous interactions (Xic:Xic, PAR:PAR, Xic:PAR). Xic pairing occurs within the tetrad. Depleting PAR-TERRA abrogates pairing and blocks initiation of XCI, whereas autosomal PAR-TERRA induces ectopic pairing. We proposed a Constrained Diffusion Model in which PAR-TERRA creates an interaction hub to guide Xic homology searching during XCI.en-USJournal Article2018-02-2610.1038/nsmb.3432