| Literature DB >> 28692038 |
Hsueh-Ping Chu1,2,3, John E Froberg1,2,3, Barry Kesner1,2,3, Hyun Jung Oh1,2,3, Fei Ji2,4, Ruslan Sadreyev2,4, Stefan F Pinter1,2,3, Jeannie T Lee1,2,3.
Abstract
In mammals, homologous chromosomes rarely pair outside meiosis. One 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 (ES) cells. The subtelomeric, pseudoautosomal regions (PARs) of the two sex chromosomes (X and Y) also undergo pairing in both female and male cells. PARs transcribe 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 to the PAR and Xic. During X-chromosome pairing, PAR-TERRA anchors the Xic to the PAR, creating a 'tetrad' of pairwise homologous interactions (Xic-Xic, PAR-PAR, and 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 propose a 'constrained diffusion model' in which PAR-TERRA creates an interaction hub to guide Xic homology searching during XCI.Entities:
Mesh:
Substances:
Year: 2017 PMID: 28692038 PMCID: PMC5553554 DOI: 10.1038/nsmb.3432
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN: 1545-9985 Impact factor: 15.369