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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6157-6173.e24
JournalCell
Volume184
Issue number25
DOIs
Publication statusPublished - 9 Dec 2021
Externally publishedYes

Keywords

  • 3D genome
  • chromatin loop
  • chromosome conformation
  • CTCF
  • CTCF release factor
  • CTCF site selection
  • gene activation
  • Jpx RNA
  • loop anchors
  • noncoding RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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