PAR-TERRA directs homologous sex chromosome pairing
Autor: | Barry Kesner, John E. Froberg, Hyun Jung Oh, Fei Ji, Hsueh-Ping Chu, Ruslan I. Sadreyev, Stefan F. Pinter, Jeannie T. Lee |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Transcription Genetic Pseudoautosomal region Biology Article X-inactivation Mice 03 medical and health sciences 0302 clinical medicine Meiosis X Chromosome Inactivation Structural Biology Homologous chromosome Animals Molecular Biology X chromosome Pseudoautosomal Regions Genetics Sex Chromosomes Dosage compensation Telomere DNA-Binding Proteins Chromosome Pairing 030104 developmental biology Pairing 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Nature structural & molecular biology |
ISSN: | 1545-9985 1545-9993 |
Popis: | 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. |
Databáze: | OpenAIRE |
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