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ELF3 activated by a super-enhancer and an autoregulatory feedback loop is required for high level HLA-C expression on extravillous trophoblasts

ABSTRACT: ELF3 activated by a super-enhancer and an autoregulatory feedback loop is required for high level HLA-C expression on extravillous trophoblasts

PROVIDER: PRJNA694844 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13529705_1.fastq.gz	Fastqsanger.gz
	SRR13529705_2.fastq.gz	Fastqsanger.gz
	SRR13529706_1.fastq.gz	Fastqsanger.gz
	SRR13529706_2.fastq.gz	Fastqsanger.gz
	SRR13529707_1.fastq.gz	Fastqsanger.gz

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ELF3 activated by a super-enhancer and an autoregulatory feedback loop is required for high level HLA-C expression on extravillous trophoblasts

Project description:HLA-C arose during evolution of pregnancy in the Great Apes 10-15 million years ago. It has a dual function on placental extravillous trophoblasts (EVT) as it contributes to both tolerance and immunity at the maternal-fetal interface. The mode of its regulation is of considerable interest in connection with the biology of pregnancy and pregnancy abnormalities. First trimester primary EVT in which HLA-C is highly expressed, as well as JEG3, an EVT model cell lines, were employed. Single cell RNA-seq data and quantitative PCR identified high expression of the transcription factor ELF3 in those cells. ChIP-PCR confirmed that both ELF3 and MED1 bound to the proximal HLA-C promoter region. However, binding of RFX5 to this region was absent or severely reduced and the adjacent HLA-B locus remained closed. Expression of HLA-C was inhibited by ELF3 siRNAs and by wrenchnolol treatment. Wrenchnolol is a cell-permeable synthetic organic molecule that mimics ELF3 and is relatively specific for binding to ELF3’s coactivator, MED23, as our data also showed in JEG3. Moreover, the ELF3 gene is regulated by a super-enhancer that spans more than 5 Mb, identified by ATAC-seq, as well as by its sensitivity to (+)-JQ1 (inhibitor of BRD4). ELF3 bound to its own promoter, thus creating an autoregulatory feedback loop that establishes expression of ELF3 and HLA-C in trophoblasts. Wrenchnolol blocked binding of MED23 to ELF3, thus disrupting the positive feedback loop that drives ELF3 expression, with down regulation of HLA-C expression as a consequence.

2021-01-27 | GSE165511 | GEO

ELF3 activated by a super-enhancer and an autoregulatory feedback loop is required for high level HLA-C expression on extravillous trophoblasts

Project description:ELF3 activated by a super-enhancer and an autoregulatory feedback loop is required for high level HLA-C expression on extravillous trophoblasts

| PRJNA694844 | 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

Effect of ELF3 and NLRP7 depletion on gene expression in JEG-3 cells

Project description:The distinct Class I MHC expression pattern in extravillous trophoblasts (EVT) endows them with immune-tolerant properties that enable successful pregnancy. Notwithstanding, it remains elusive how this process is elaborately regulated. Previously, we identified ELF3 as a transcription factor that governs high level HLA-C expression in EVT. In this study, we found that ELF3 also binds to the enhancer region of two NLR genes, NLRP2 and NLRP7, transactivating NLRP7 expression while suppressing expression of NLRP2. We confirmed that NLRP2 suppresses HLA-C expression while in this study we described a novel role for NLRP7 promoting HLA-C expression in trophoblasts. These two NLR genes, highly expressed in trophoblasts, are thus fine-tuned by ELF3 and enable proper expression of HLA-C in trophoblasts.

2023-09-05 | GSE241792 | GEO

ELF3 activated by a superenhancer and an autoregulatory feedback loop is required for high-level HLA-C expression on extravillous trophoblasts.

Project description:HLA-C arose during evolution of pregnancy in the great apes 10 to 15 million years ago. It has a dual function on placental extravillous trophoblasts (EVTs) as it contributes to both tolerance and immunity at the maternal-fetal interface. The mode of its regulation is of considerable interest in connection with the biology of pregnancy and pregnancy abnormalities. First-trimester primary EVTs in which HLA-C is highly expressed, as well as JEG3, an EVT model cell line, were employed. Single-cell RNA-seq data and quantitative PCR identified high expression of the transcription factor ELF3 in those cells. Chromatin immunoprecipitation (ChIP)-PCR confirmed that both ELF3 and MED1 bound to the proximal HLA-C promoter region. However, binding of RFX5 to this region was absent or severely reduced, and the adjacent HLA-B locus remained closed. Expression of HLA-C was inhibited by ELF3 small interfering RNAs (siRNAs) and by wrenchnolol treatment. Wrenchnolol is a cell-permeable synthetic organic molecule that mimics ELF3 and is relatively specific for binding to ELF3's coactivator, MED23, as our data also showed in JEG3. Moreover, the ELF3 gene is regulated by a superenhancer that spans more than 5 Mb, identified by assay for transposase-accessible chromatin using sequencing (ATAC-seq), as well as by its sensitivity to (+)-JQ1 (inhibitor of BRD4). ELF3 bound to its own promoter, thus creating an autoregulatory feedback loop that establishes expression of ELF3 and HLA-C in trophoblasts. Wrenchnolol blocked binding of MED23 to ELF3, thus disrupting the positive-feedback loop that drives ELF3 expression, with down-regulation of HLA-C expression as a consequence.

| S-EPMC7936349 | biostudies-literature

Extravillous trophoblast and endothelial cell crosstalk mediates leukocyte infiltration to the early remodelling decidual spiral arteriole wall

Project description:Decidual spiral arteriole (SpA) remodelling is essential to ensure optimal uteroplacental blood flow during human pregnancy. Decidual uterine natural killer cells and macrophages infiltrate the SpA and are proposed to initiate remodelling before colonisation by extravillous trophoblasts. Microarrays were used to measure the effect of extravillous trophoblasts conditioned medium on the transcriptome of human uterine microvascular endothelial cells.

2017-10-16 | E-MTAB-5467 | biostudies-arrayexpress

RRBS investigation of matched side-population trophoblast, cytotrophoblast and extravillous trophoblast populations from 4 human placentae

Project description:To better understand how DNA methylation influences placentation, DNA from first trimester primary trophoblast populations (side-population trophoblasts, cytotrophoblasts and extravillous trophoblasts) isolated using FACS underwent reduced representation bisulfite sequencing and were compared to publicly available data of blastocyst-derived and somatic cell populations.

2018-12-25 | GSE109682 | GEO

Zika virus impacts extracellular vesicle composition and cellular gene expression in macaque early gestation trophoblasts

Project description:Zika virus (ZIKV) infection at the maternal-placental interface is associated with adverse pregnancy outcomes including fetal demise and pregnancy loss. To determine how infection impacts placental trophoblasts, we utilized rhesus macaque trophoblast stem cells (TSC) that can be differentiated into early gestation syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT). TSCs and STs, but not EVTs, were highly permissive to productive infection with ZIKV strain DAK AR 41524. The impact of ZIKV on the cellular transcriptome showed that infection of TSCs and STs increased expression of immune related genes, including those involved in type I and type III interferon responses. ZIKV exposure altered extracellular vesicle (EV) protein, mRNA, and miRNA cargo, regardless of productive infection. These findings suggest that early gestation macaque TSCs and STs are permissive to ZIKV infection, and that EV analysis may provide a foundation for identifying non-invasive biomarkers of placental infection in a highly translational model.

2022-05-20 | PXD033289 | Pride

An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [CUT&RUN]

Project description:An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [CUT&RUN]

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An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [ChIP-seq]

Project description:An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [ChIP-seq]

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