Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops

Hyun Jung Oh, Rodrigo Aguilar, Barry Kesner, Hun Goo Lee, Andrea J. Kriz, Hsueh Ping Chu, Jeannie T. Lee

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

5 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)6157-6173.e24
PublicaciónCell
Volumen184
N.º25
DOI
EstadoPublicada - 9 dic. 2021
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Bioquímica, genética y biología molecular (todo)

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