The role of GRHL2 and epigenetic remodeling in epithelial–mesenchymal plasticity in ovarian cancer cells

Vin Yee Chung, Tuan Zea Tan, Jieru Ye, Rui Lan Huang, Hung Cheng Lai, Dennis Kappei, Heike Wollmann, Ernesto Guccione, Ruby Yun Ju Huang

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number272
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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ovarian neoplasms
Epigenomics
epigenetics
Ovarian Neoplasms
Plasticity
Genes
Cells
Histone Code
Azacitidine
Methylation
Phase Transition
Gene Expression Profiling
DNA methylation
DNA Methylation
phase transition
phenotypic plasticity
transcriptomics
histones
methylation
Histones

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

The role of GRHL2 and epigenetic remodeling in epithelial–mesenchymal plasticity in ovarian cancer cells. / Chung, Vin Yee; Tan, Tuan Zea; Ye, Jieru; Huang, Rui Lan; Lai, Hung Cheng; Kappei, Dennis; Wollmann, Heike; Guccione, Ernesto; Huang, Ruby Yun Ju.

In: Communications Biology, Vol. 2, No. 1, 272, 01.12.2019.

Research output: Contribution to journalArticle

Chung, Vin Yee ; Tan, Tuan Zea ; Ye, Jieru ; Huang, Rui Lan ; Lai, Hung Cheng ; Kappei, Dennis ; Wollmann, Heike ; Guccione, Ernesto ; Huang, Ruby Yun Ju. / The role of GRHL2 and epigenetic remodeling in epithelial–mesenchymal plasticity in ovarian cancer cells. In: Communications Biology. 2019 ; Vol. 2, No. 1.
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