Effects of topological domain disruption on transcriptional regulation are chromatin context dependent.

ABSTRACT:

Background

Three-dimensional genome organization helps coordinate enhancer-promoter communication while insulating loci from inappropriate regulatory contacts. CTCF and cohesin contribute to this organization by forming topologically associating domains. However, how boundary elements at individual loci influence transcription remains context dependent.

Results

We investigated the conserved topological organization of the mammalian NOTCH1 locus. Across human cell types, NOTCH1 resides within a defined topologically associated domain with CTCF/cohesin occupancy at both 5' and 3' boundaries. In human K562 cells, CRISPR-Cas9 deletion of boundary CTCF sites increased transcription of NOTCH1 and the intradomain non-coding transcripts NALT1 and LINC01451. Boundary perturbations im

SUBMITTER: Cerecedo-Castillo AJ 

PROVIDER: S-EPMC12933966 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature