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Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118408 | GEO | 2019/08/06

REPOSITORIES: GEO

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Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [MethylArray]

Project description:Ovarian cancer (OC) cells exhibit varying extents of epithelial/mesenchymal phenotype, forming an EMT spectrum based on their EMT scores. Combining 450K DNA methylation array, ChIP-sequencing of five histone H3 marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptomic analyses, we examined the genome-wide epigenetic profiles of OC cell lines with progressive EMT phenotypes, including a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2) which showed intermediate state transition. We identified differentially methylated CpG sites (DMCs) associated with EMT genes, found mainly at the promoters of epithelial genes including CDH1, GRHL2 and genes with GRHL2 binding sites. This prompted us to further study the epigenetic role of GRHL2. GRHL2-knockdown resulted in CpG methylation gain at GRHL2 binding sites and at DMCs associated with epithelial genes. Importantly, the changes of histone modifications occurred in GRHL2-knockdown cells are also more prominent among epithelial genes and at GRHL2 binding sites—reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3—similar to the transitions observed in a four-cell-line model representing the EMT spectrum. We tested the effects of GRHL2 overexpression in conjunction with epigenetic drugs 5-azacitidine, GSK126 and mocetinostat, all of which exerted MET effects to different extents, depending on the existing cell state. Overall, GRHL2 is required for the epigenetic and chromatin remodeling of epithelial genes during EMT/MET that control intermediate phenotype switching.

2019-08-06 | GSE118405 | GEO

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ExpressionArray]

2019-08-06 | GSE118171 | GEO

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [RNA-seq]

2019-08-06 | GSE118407 | GEO

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ChIP-seq]

2019-08-06 | GSE118406 | GEO

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition

Project description:Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition

| PRJNA485485 | ENA

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [MethylArray]

Project description:Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [MethylArray]

| PRJNA485490 | ENA

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ExpressionArray]

Project description:Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ExpressionArray]

| PRJNA484762 | ENA

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ChIP-seq]

Project description:Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [ChIP-seq]

| PRJNA485491 | ENA

Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [RNA-seq]

Project description:Grainyhead-like 2 (GRHL2) and epigenetic remodeling in the intermediate states of epithelial-mesenchymal transition [RNA-seq]

| PRJNA485494 | ENA

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

Project description: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.

| S-EPMC6656769 | biostudies-literature

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