The Role of GRHL2 and Epigenetic Remodeling in Epithelial-mesenchymal Plasticity in Ovarian Cancer Cells

Overview

Journal Commun Biol

Specialty Biology

Date 2019 Aug 3

PMID 31372511

Citations 48

Authors

Vin Yee Chung

Tuan Zea Tan

Jieru Ye

Rui-Lan Huang

Hung-Cheng Lai

Dennis Kappei

Heike Wollmann

Ernesto Guccione

Ruby Yun-Ju Huang

Affiliations

Soon will be listed here.

Abstract

Cancer cells exhibit phenotypic plasticity during epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) involving intermediate states. To study genome-wide epigenetic remodeling associated with EMT plasticity, we integrate the analyses of DNA methylation, ChIP-sequencing of five histone marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptome profiling performed on ovarian cancer cells with different epithelial/mesenchymal states and on a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2). We have identified differentially methylated CpG sites associated with EMT, found at promoters of epithelial genes and GRHL2 binding sites. GRHL2 knockdown results in CpG methylation gain and nucleosomal remodeling (reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3), resembling the changes observed across progressive EMT states. Epigenetic-modifying agents such as 5-azacitidine, GSK126 and mocetinostat further reveal cell state-dependent plasticity upon GRHL2 overexpression. Overall, we demonstrate that epithelial genes are subject to epigenetic control during intermediate phases of EMT/MET involving GRHL2.

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