Premium
Dynamic cohesin‐mediated chromatin architecture controls epithelial–mesenchymal plasticity in cancer
Author(s) -
Yun Jiyeon,
Song SangHyun,
Kim HwangPhill,
Han SaeWon,
Yi Eugene C,
Kim TaeYou
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201541852
Subject(s) - medicine , library science , political science , computer science
Epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET) are important interconnected events in tumorigenesis controlled by complex genetic networks. However, the cues that activate EMT‐initiating factors and the mechanisms that reversibly connect EMT/MET are not well understood. Here, we show that cohesin‐mediated chromatin organization coordinates EMT/MET by regulating mesenchymal genes. We report that RAD21, a subunit of the cohesin complex, is expressed in epithelial breast cancer cells, whereas its expression is decreased in mesenchymal cancer. Depletion of RAD21 in epithelial cancer cells causes transcriptional activation of TGFB1 and ITGA5 , inducing EMT. Reduced binding of RAD21 changes intrachromosomal chromatin interactions within the TGFB1 and ITGA5 loci, creating an active transcriptional environment. Similarly, stem cell‐like cancer cells also show an open chromatin structure at both genes, which correlates with high expression levels and mesenchymal fate characteristics. Conversely, overexpression of RAD21 in mesenchymal cancer cells induces MET‐specific expression patterns. These findings indicate that dynamic cohesin‐mediated chromatin structures are responsible for the initiation and regulation of essential EMT‐related cell fate changes in cancer.