DOI: 10.1101/495432Dec 13, 2018Paper

An RNA-binding region regulates CTCF clustering and chromatin looping

BioRxiv : the Preprint Server for Biology
Anders S HansenRobert Tjian

Abstract

Mammalian genomes are folded into Topologically Associating Domains (TADs), consisting of cell-type specific chromatin loops anchored by CTCF and cohesin. Since CTCF and cohesin are expressed ubiquitously, how cell-type specific CTCF-mediated loops are formed poses a paradox. Here we show RNase-sensitive CTCF self-association in vitro and that an RNA-binding region (RBR) mediates CTCF clustering in vivo. Intriguingly, deleting the RBR abolishes or impairs almost half of all chromatin loops in mouse embryonic stem cells. Disrupted loop formation correlates with abrogated clustering and diminished chromatin binding of the RBR mutant CTCF protein, which in turn results in a failure to halt cohesin-mediated extrusion. Thus, CTCF loops fall into at least 2 classes: RBR-independent and RBR-dependent loops. We suggest that evidence for distinct classes of RBR-dependent loops may provide a mechanism for establishing cell-specific CTCF loops regulated by RNAs and other RBR partners.

Related Concepts

Allergens
Chromatin
Genome
Laboratory mice
RNA
RNA-Binding Proteins
Loop
CCCTC-binding factor
Cohesins
Chromatin Binding

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