Journal Article

Cohesin-mediated interactions organize chromosomal domain architecture

Georgopoulou, Dimitra, Chan, Wen‐Ching, Hadjur, Suzana, Vietri Rudan, Matteo, Schroth, Gary P, Sofueva, Sevil, Mira‐Bontenbal, Hegias, Pollard, Steven M, Tanay, Amos, Yaffe, Eitan

2013

Overview

To ensure proper gene regulation within constrained nuclear space, chromosomes facilitate access to transcribed regions, while compactly packaging all other information. Recent studies revealed that chromosomes are organized into megabase‐scale domains that demarcate active and inactive genetic elements, suggesting that compartmentalization is important for genome function. Here, we show that very specific long‐range interactions are anchored by cohesin/CTCF sites, but not cohesin‐only or CTCF‐only sites, to form a hierarchy of chromosomal loops. These loops demarcate topological domains and form intricate internal structures within them. Post‐mitotic nuclei deficient for functional cohesin exhibit global architectural changes associated with loss of cohesin/CTCF contacts and relaxation of topological domains. Transcriptional analysis shows that this cohesin‐dependent perturbation of domain organization leads to widespread gene deregulation of both cohesin‐bound and non‐bound genes. Our data thereby support a role for cohesin in the global organization of domain structure and suggest that domains function to stabilize the transcriptional programmes within them. Chromosomal compartmentalization has been recognized as important for genome function. High‐resolution techniques such as Hi‐C, ChIP‐ and 4C‐seq offer novel insights into cohesin's dynamic role in shaping the nuclear architecture.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V
• Subject: Animals / Catalytic Domain / CCCTC-Binding Factor / Cell Cycle Proteins - chemistry / Cell Cycle Proteins - genetics / Cell Cycle Proteins - metabolism / Cell Proliferation / Cells, Cultured / Chromosomal Proteins, Non-Histone - chemistry / Chromosomal Proteins, Non-Histone - genetics / Chromosomal Proteins, Non-Histone - metabolism / chromosome organization / Chromosomes / Chromosomes - chemistry / Chromosomes - metabolism / cohesin / Cohesins / Deregulation / DNA-Binding Proteins / EMBO11 / EMBO13 / Gene Expression Regulation / Genetics / Mice / Mitosis / Molecular biology / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / Packaging / Phosphoproteins - genetics / Phosphoproteins - metabolism / Repressor Proteins - metabolism / Stem Cells - physiology / transcription / Transcription, Genetic