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An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (Affymetrix data set)

ABSTRACT: The role of Gata2 in regulating the expression of HLA in human decidual stromal cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE108407 | GEO | 2018/01/02

SECONDARY ACCESSION(S): PRJNA427169

REPOSITORIES: GEO

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An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (ChIP-Seq data set)

Project description:The role of Gata2 in regulating the expression of HLA in huamn decidual stromal cells

2018-01-02 | GSE108408 | GEO

An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.

Project description:Variation in female reproductive traits, such as fertility, fecundity, and fecundability, are heritable in humans, but identifying and functionally characterizing genetic variants associated with these traits have been challenging. Here, we explore the functional significance and evolutionary history of a G/A polymorphism at SNP rs2523393, which is an eQTL for HLA-F and is significantly associated with fecundability (the probability of being pregnant within a single menstrual cycle). We replicated the association between the rs2523393 genotype and HLA-F expression by using GTEx data and demonstrate that HLA-F is upregulated in the endometrium during the window of implantation and by progesterone in decidual stromal cells. Next, we show that the rs2523393 A allele creates a GATA2 binding site in a progesterone-responsive distal enhancer that loops to the HLA-F promoter. Remarkably, we found that the A allele is derived in the human lineage and that the G/A polymorphism arose before the divergence of modern and archaic humans and segregates at intermediate to high frequencies across human populations. Remarkably, the derived A allele is has also been identified in a GWAS as a risk allele for multiple sclerosis. These data suggest that the polymorphism is maintained by antagonistic pleiotropy and a reproduction-health tradeoff in human evolution.

| S-EPMC6174278 | biostudies-literature

An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-01-02 | GSE108409 | GEO

An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F

Project description:An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F

| PRJNA427162 | ENA

An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (Affymetrix data set)

Project description:An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (Affymetrix data set)

| PRJNA427169 | ENA

An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (ChIP-Seq data set)

Project description:An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (ChIP-Seq data set)

| PRJNA427171 | ENA

Transcriptional characterization of primary human HLA-G+ extravillous trophoblasts (EVT) and Villous trophoblasts (VT)

Project description:Seven patient paired primary human HLA-G+ extravillous trophoblasts (EVT) and Villous trophoblasts (VT) obtained from 1st trimester (7-9 weeks) villous tissue were obtained. RNA was isolated directly after isolation and purification using FACS sort for CD45-HLA-G+ (EVT) and CD45-HLA-G-EGFR1+ (VT) fractions. Expression profiles were compared to two samples of the choriocarcinoma cell line JEG-3 and four samples of decidual stromal cells (DSC) at passage 2 after cell culture.

2015-05-15 | E-MTAB-3217 | biostudies-arrayexpress

Gata2 is a master regulator of endometrial function and progesterone signaling [Affymetrix]

Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration. Gata2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Gata2fl/fl (termed Gata2d/d) uterus. While littermate controls are fertile, Gata2d/d females are completely infertile. Analysis of the infertility indicates that implantation does not occur, and the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Measure of P4 target genes including PR itself indicate a block in P4 target gene induction and that Gata2 regulates PR expression directly. Microarray analysis demonstrates that ablation of Gata2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and Ihh signaling pathway. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.Taken together, these data demonstrate that Gata2 is a critical regulator of gene expression and function in the murine uterus.

2014-01-01 | E-GEOD-40660 | biostudies-arrayexpress

Gata2 is a master regulator of endometrial function and progesterone signaling [ChIP-Seq]

2014-01-01 | E-GEOD-40659 | biostudies-arrayexpress

The role of chorionic PGRMC2 and HLA-G in maintaining immune homeostasis at the chorio-decidual interface

Project description:The chorio-decidual interface (CDi) is formed by chorion trophoblasts (CTCs) and immune cell-rich decidua (DECs) cells. The roles of human leukocyte antigen (HLA)-G and progesterone receptor membrane component 2 (PGRMC2) in mediating innate immune homeostasis at this maternal-fetal interface interface were investigated.

2024-01-02 | GSE251809 | GEO

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