MCM complexes are barriers that restrict cohesin-mediated loop extrusion.

ABSTRACT: Eukaryotic genomes are compacted into loops and topologically associating domains (TADs)^1-3, which contribute to transcription, recombination and genomic stability^4,5. Cohesin extrudes DNA into loops that are thought to lengthen until CTCF boundaries are encountered^6-12. Little is known about whether loop extrusion is impeded by DNA-bound machines. Here we show that the minichromosome maintenance (MCM) complex is a barrier that restricts loop extrusion in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture) of mouse zygotes reveals that MCM loading reduces CTCF-anchored loops and decreases TAD boundary insulation, which suggests that loop extrusion is impeded before reaching CTCF. This effect extends to HCT116 cells, in which MCMs

SUBMITTER: Dequeker BJH 

PROVIDER: S-EPMC9159944 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature