Regulation of cohesin‐mediated chromosome folding by PDS5 in mammals

• Published in: EMBO reports Vol. 23; no. 11; pp. e54853 - n/a
• Main Authors: Yu, Dingdang, Chen, Guoyu, Wang, Yuci, Wang, Yining, Lin, Risheng, Liu, Nanbo, Zhu, Ping, Liu, Hang, Hu, Tao, Feng, Rui, Feng, Haizhong, Lan, Fei, Cai, Jiabin, Chen, Hao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2022; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Animals; Cell Cycle Proteins - metabolism; Chromatin; Chromatin - genetics; chromatin loop; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Chromosomes; Chromosomes - genetics; Chromosomes - metabolism; Cohesin; Cohesins; Cohesion; CTCF; Depletion; EMBO09; Folding; Hepatocytes; Liver cancer; loop extrusion; Mammals; Mammals - genetics; Mammals - metabolism; PDS5; Proteins; Vertebrates; chromatin loop; cohesin; PDS5; CTCF; loop extrusion
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.202254853

Cohesin regulates sister chromatid cohesion but also contributes to chromosome folding by promoting the formation of chromatin loops, a process mediated by loop extrusion. Although PDS5 regulates cohesin dynamics on chromatin, the exact function of PDS5 in cohesin‐mediated chromatin looping remains unclear. Two paralogs of PDS5 exist in vertebrates, PDS5A and PDS5B. Here we show that PDS5A and PDS5B co‐localize with RAD21 and CTCF at loop anchors. Rapid PDS5A or PDS5B degradation in liver cancer cells using an inducible degron system reduces chromatin loops and increases loop size. RAD21 enrichment at loop anchors is decreased upon depletion of PDS5A or PDS5B. PDS5B loss also reduces CTCF signals at loop anchors and has a stronger effect on loop enlargement compared with PDS5A. Co‐depletion of PDS5A and PDS5B reduces RAD21 levels at loop anchors although the amount of cohesin on chromatin is increased. Our study provides insight into how PDS5 proteins regulate cohesin‐mediated chromatin looping. Synopsis PDS5 proteins stabilize cohesin at loop anchors, facilitate chromatin loop formation and restrict loop expansion in mammals. PDS5 proteins stabilize cohesin‐mediated chromatin loops. PDS5 proteins limit loop size. PDS5 proteins and CTCF together define loop anchors. Graphical Abstract PDS5 proteins stabilize cohesin at loop anchors, facilitate chromatin loop formation and restrict loop expansion in mammals.