Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection.

ABSTRACT:

Background

CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem.

Results

Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglob

SUBMITTER: Jia Z 

PROVIDER: S-EPMC7087399 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature