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Analysis of the Phosphorylated Estrogen Receptor-α Cistrome Reveals Association with Direct ER-DNA Binding and the Transcription Factor GRHL2

ABSTRACT: Analysis of the Phosphorylated Estrogen Receptor-α Cistrome Reveals Association with Direct ER-DNA Binding and the Transcription Factor GRHL2

PROVIDER: PRJNA482473 | ENA |

REPOSITORIES: ENA

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Analysis of the Phosphorylated Estrogen Receptor-α Cistrome Reveals Association with Direct ER-DNA Binding and the Transcription Factor GRHL2

Project description:Phosphorylation of the estrogen receptor-α (ER) at serine 118 (pS118-ER) is involved in modulating ER-dependent gene transcription and recruitment of ER to certain gene promoters. While the effects of pS118 on ER-DNA interactions have been investigated at specific sites, the genome-wide binding profile (cistrome) of pS118-ER remains to be studied. To characterize the pS118-ER cistrome, ChIP-seq was performed on pS118-ER and pan-ER in MCF-7 cells. A subset of ER sites was occupied by pS118-ER and these sites were associated with the active enhancer mark H3K27ac. Additionally, pS118-ER sites were found to be enriched in the DNA binding motif for GRHL2 as well as the estrogen response element relative to all ER sites. Utilizing a DNA binding microarray, pS118-ER was found to be more commonly associated with direct DNA binding events compared to indirect binding events. These results suggest a role for pS118-ER at active enhancers and as a regulator of direct ER-DNA interactions.

2018-12-11 | GSE117569 | GEO

The Phosphorylated Estrogen Receptor ? (ER) Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2.

Project description: Not available

| S-EPMC6336141 | biostudies-literature

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [RNA-seq]

Project description:Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) is induced by estrogen and is the most abundant post-translational mark associated with a transcriptionally active receptor. Cistromic analysis of pS118-ER from our group found enrichment of the GRHL2 motif near pS118-ER binding sites. In this report we use cistromic and transcriptomic analyses to interrogate the relationship between GRHL2 and pS118-ER. We found that GRHL2 is bound to chromatin at pS118-ER/GRHL2 co-occupancy sites prior to ligand treatment, and GRHL2 binding is required for maximal pS118-ER recruitment. pS118-ER/GRHL2 co-occupancy sites were enriched at active enhancers marked by H3K27ac and H3K4me1, along with FOXA1 and p300. Transcriptomic analysis yielded four subsets of ER/GRHL2 co-regulated genes revealing that GRHL2 can both enhance and antagonize E2-mediated ER transcriptional activity. Gene ontology analysis identified several coregulated genes involved in cell migration. Accordingly, knockdown of GRHL2 combined with estrogen treatment resulted in increased cell migration but no change in proliferation. These results support a model in which GRHL2 binds to select enhancers and facilitates pS118-ER recruitment to chromatin which then results in differential activation and repression of genes that control ER-positive breast cancer cell migration.

2022-05-19 | GSE202621 | GEO

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression[ChIP-seq]

2022-05-19 | GSE202620 | GEO

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [Cut&Run]

2022-05-19 | GSE202619 | GEO

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression

Project description:GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression

| PRJNA836788 | ENA

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [Cut&Run]

Project description:GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [Cut&Run]

| PRJNA836800 | ENA

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [RNA-seq]

Project description:GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression [RNA-seq]

| PRJNA836798 | ENA

GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression[ChIP-seq]

Project description:GRHL2 enhances phosphorylated estrogen receptor DNA binding and regulates ER-mediated transcriptional activation and repression[ChIP-seq]

| PRJNA836799 | ENA

Effect of GRHL2 in HMLE+Twist-ER+4-OHT cells

Project description:Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF-β-dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT. Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines. Functionally, GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells. These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter. GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF-β receptor antagonist, BMP2. The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis. These results indicate that GRHL2 is a suppressor of the oncogenic EMT. 3 biologic replicates for each cell line. Comparison of HMLE+Twist-ER cells expressing GRHL2/pMIG vs. HMLE+Twist-ER cells expressing empty pMIG.

2012-02-25 | E-GEOD-36081 | biostudies-arrayexpress

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