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Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops
Ist Teil von
Cell, 2021-12, Vol.184 (25), p.6157-6173.e24
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2021
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
Chromosome loops shift dynamically during development, homeostasis, and disease. CCCTC-binding factor (CTCF) is known to anchor loops and construct 3D genomes, but how anchor sites are selected is not yet understood. Here, we unveil Jpx RNA as a determinant of anchor selectivity. Jpx RNA targets thousands of genomic sites, preferentially binding promoters of active genes. Depleting Jpx RNA causes ectopic CTCF binding, massive shifts in chromosome looping, and downregulation of >700 Jpx target genes. Without Jpx, thousands of lost loops are replaced by de novo loops anchored by ectopic CTCF sites. Although Jpx controls CTCF binding on a genome-wide basis, it acts selectively at the subset of developmentally sensitive CTCF sites. Specifically, Jpx targets low-affinity CTCF motifs and displaces CTCF protein through competitive inhibition. We conclude that Jpx acts as a CTCF release factor and shapes the 3D genome by regulating anchor site usage.
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•Jpx RNA binds and activates hundreds of mammalian genes in the mouse genome•Jpx selectively evicts CTCF bound to low-affinity, developmentally sensitive sites•Jpx loss causes genome-wide shifts in CTCF binding and chromosome looping•Jpx determines anchor site usage by serving as a CTCF release factor
Jpx RNA regulates chromosome looping throughout the genome by releasing CTCF from chromatin, thereby determining where CTCF binds, how anchor sites are selected, and how genome architecture is regulated.