Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops
Journal
Cell
Journal Volume
184
Journal Issue
25
Pages
6157 - 6173.e24
Date Issued
2021-12-09
Author(s)
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.
Subjects
3D genome
chromatin loop
chromosome conformation
CTCF
CTCF release factor
CTCF site selection
gene activation
Jpx RNA
loop anchors
noncoding RNA
Publisher
Elsevier B.V.
Type
journal issue