Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE296935 | GEO | 2025/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN]

Project description:Progesterone, acting through its isoform receptors PGR-A and PGR-B, is essential for regulating uterus function. The ratio between these isoforms is dynamic and context-dependent, driving distinct transcriptional programs. The upstream mechanisms controlling the PGR isoform balance and their functional impact in the uterus remain poorly understood. In this study, we identified two distal PGR enhancers in endometrial stromal cells located 60 kb and 220 kb upstream of the PGR transcription start site. We found that in comparison to PGR promoter-targeting which favors a PGR-B dominant profile, activation of these enhancers shifts the isoform ratio by increasing PGR-A and decreasing PGR-B expression. Bulk RNA-sequencing revealed that the isoform balance alters the progesterone-regulated transcriptome. PGR-A/B-equivalent cells displayed pro-inflammatory gene signatures, whereas PGR-B-dominant cells exhibited suppression of inflammatory signaling and cell cycle activity. Cut&Run assays identified differential genomic binding patterns associated with each isoform profile, and integration with chromatin interaction maps suggest direct regulation of distinct gene subsets. Upstream, ESR1 indirectly activated the PGR-A isoform dominantly, potentially through cooperation with FOXO1 at the U2 enhancer. This study identifies a novel enhancer-driven mechanism regulating PGR isoform dynamics and sheds light on how their imbalance in the endometrial stroma may reshape progesterone signaling in health and disease.

2025-09-30 | GSE296932 | GEO

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [RNA-Seq]

2025-09-30 | GSE296931 | GEO

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN 2]

2025-09-30 | GSE296934 | GEO

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells

Project description:PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells

| PRJNA1261947 | ENA

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN]

Project description:PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN]

| PRJNA1261955 | ENA

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [RNA-Seq]

Project description:PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [RNA-Seq]

| PRJNA1261952 | ENA

PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN 2]

Project description:PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN 2]

| PRJNA1261956 | ENA

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

Project description:We report the genome-wide binding sites of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells that express either PGR-A or PGR-B. Progesterone, acting through the progesterone receptors (PGRs), is one of the most critical regulators of endometrial differentiation, known as decidualization, which is a key step toward the establishment of pregnancy. Yet a long-standing unresolved issue in uterine biology is the precise roles played by the major PGR isoforms, PGR-A and PGR-B, during decidualization in the human. Our approach, expressing PGR-A and PGR-B individually after silencing endogenous PGRs in human endometrial stromal cells (HESC), enabled the analysis of the roles of these isoforms separately as well as jointly by ChIP-seq and gene-expression analysis. In order to study the cistromes of PGR-A and PGR-B at 2h of in vitro differentiation of human endometrial stromal cells, we generated primary cultures of human endometrial stromal cells expressing flag tagged PGR-A and PGR-B individually after silencing endogenous PGRs. Input DNA was used as the reference sample.

2015-04-27 | E-GEOD-62475 | biostudies-arrayexpress

Genome-wide binding sites of Progesterone receptor (PGR) isoforms PGR-A and PGR-B during differentiation of human endometrial stromal cells

2015-04-27 | GSE62475 | GEO

Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes.

Project description:Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines. R5020 (10nM-10μM range) induced dose-dependent PR mRNA and protein expression in the absence of estrogen but required both PR and ERα. Antagonists of either PR (RU486, onapristone) or ERα (ICI 182,780) attenuated R5020 induction of TFF1, CTSD, and PGR. Chromatin immunoprecipitation (ChIP) assays performed on ER+/PR+ cells demonstrated that both ERα and PR were recruited to the same ERE/Sp1 site-containing region of the PGR proximal promoter in response to high dose progestin (10μM). Recruitment of ERα and PR to chromatin and subsequent PR mRNA induction were dependent upon rapid activation of MAPK/ERK and AKT; inhibition of these kinase pathways via U0126 or LY294002 blocked these events. Overall, we have identified a novel mechanism of ERα activation initiated by rapid PR-dependent kinase pathway activation and associated with phosphorylation of ERα Ser118 for estrogen-independent but progestin-dependent ER/PR cross talk. These studies may provide insight into mechanisms of persistent ER-target gene expression during periods of hormone (i.e. estrogen) ablation and suggest caution following prolonged treatment with aromatase or CYP17 inhibitors (i.e. contexts when progesterone levels may be abnormally elevated).

| S-EPMC5068826 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data