4.8 Article

Loop stacking organizes genome folding from TADs to chromosomes

Journal

MOLECULAR CELL
Volume 83, Issue 9, Pages 1377-+

Publisher

CELL PRESS
DOI: 10.1016/j.molcel.2023.04.008

Keywords

-

Ask authors/readers for more resources

Population-level analyses have shown the significant roles of CTCF and cohesin in mammalian genome organization. However, their contributions at the single-cell level were not fully understood until now. This study used super-resolution microscopy to explore the effects of CTCF and cohesin removal, revealing their distinct contributions to loop stacking and the organization of the genome at the single-cell level.
Although population-level analyses revealed significant roles for CTCF and cohesin in mammalian genome organization, their contributions at the single-cell level remain incompletely understood. Here, we used a super-resolution microscopy approach to measure the effects of removal of CTCF or cohesin in mouse embryonic stem cells. Single-chromosome traces revealed cohesin-dependent loops, frequently stacked at their loop anchors forming multi-way contacts (hubs), bridging across TAD boundaries. Despite these bridging interactions, chromatin in intervening TADs was not intermixed, remaining separated in distinct loops around the hub. At the multi-TAD scale, steric effects from loop stacking insulated local chromatin from ultra-long range (>4 Mb) contacts. Upon cohesin removal, the chromosomes were more disordered and increased cell-cell variability in gene expression. Our data revise the TAD-centric understanding of CTCF and cohesin and provide a multi-scale, structural picture of how they organize the genome on the sin-gle-cell level through distinct contributions to loop stacking.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available