Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.

ABSTRACT: The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes. Here we show that developmental genes and nearby clusters of CTCF sites cooperatively foster the robust insulation of regulatory domains. By genetically dissecting a couple of representative loci in mouse embryonic stem cells, we show that CTCF sites prevent undesirable enhancer-gene contacts (i.e. physical insulation), while developme

SUBMITTER: Ealo T 

PROVIDER: S-EPMC11344162 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature