CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains.

ABSTRACT: Insulators play a critical role in spatiotemporal gene regulation in animals. The evolutionarily conserved CCCTC-binding factor (CTCF) is required for insulator function in mammals, but not all of its binding sites act as insulators. Here we explore the sequence requirements of CTCF-mediated transcriptional insulation using a sensitive insulator reporter in mouse embryonic stem cells. We find that insulation potency depends on the number of CTCF-binding sites in tandem. Furthermore, CTCF-mediated insulation is dependent on upstream flanking sequences at its binding sites. CTCF-binding sites at topologically associating domain boundaries are more likely to function as insulators than those outside topologically associating domain boundaries, independently of binding strength. We demonstrate

SUBMITTER: Huang H 

PROVIDER: S-EPMC8853952 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature