Snai1-driven sequential emt changes attributed by selective chromatin enrichment of RAD21 and GRHL2
Journal
Cancers
Journal Volume
12
Journal Issue
5
Pages
1140
Date Issued
2020
Author(s)
Abstract
Over two decades of research on cancer-associated epithelial-mesenchymal transition (EMT) led us to ascertain the occurrence of transitional intermediate states (collectively referred to as the EMT spectrum). Among the molecular factors that drive EMT, SNAI1 plays an indispensable role in regulating other core transcription factors, and this regulation is highly context-dependent. However, molecular investigation on this context-dependent regulation is still lacking. Using two ovarian cancer cell lines, we show that SNAI1 regulation on other core EMT-TFs switches from a repressive control in highly epithelial cells to an activation signaling in intermediate epithelial cells. Upon further scrutiny, we identify that the expression of early epithelial genes PERP and ERBB3 are differentially regulated in SNAI1-induced sequential EMT changes. Mechanistically, we show that changes in PERP and ERBB3 transcript levels could be correlated to the selective enrichment loss of RAD21, a cohesin component, at the distal enhancer sites of PERP and ERBB3, which precedes that of the proximal promoter-associated sites. Furthermore, the RAD21 enrichment at the distal enhancer sites is dependent on GRHL2 expression. In a nutshell, the alteration of GRHL2-associated RAD21 enrichment in epithelial genes is crucial to redefine the transition of cellular states along the EMT spectrum. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Chromatin looping; Cohesin; EMT spectrum; ERBB3; GRHL2; PERP; RAD21
SDGs
Other Subjects
epidermal growth factor receptor 3; Article; binding site; chromatin immunoprecipitation; chromatin structure; controlled study; deacetylation; densitometry; down regulation; enhancer region; epithelial mesenchymal transition; epithelium cell; ERBB3 gene; fibroblast; gene; gene control; gene expression; gene identification; gene targeting; GRHL2 gene; histogram; histone acetylation; histone deacetylation; human; immunofluorescence; OVCA420 cell line; OVCA429 cell line; PERP gene; phenotype; promoter region; RAD21 gene; real time polymerase chain reaction; signal transduction; SNAI1 gene; Western blotting
Publisher
MDPI AG
Type
journal article