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The histone demethylase KDM5C represses trophoblast proliferation and invasion in woman with recurrent miscarriage [CUT & Tag]

ABSTRACT: To characterize genome-wide KDM5C traget genes in HTR-8/SVneo cells transduced with KDM5C-expression vector by CUT&Tag.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200540 | GEO | 2022/12/16

REPOSITORIES: GEO

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The histone demethylase KDM5C represses trophoblast proliferation and invasion in woman with recurrent miscarriage [RNA-seq]

Project description:KDM5C is a H3K4- specific demethylase, which has multiple biological roles in development and disease. However, the role of KDM5C in trophoblasts at the maternal-fetal interface remains unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from patient with recurrent miscarriage (RM). Trophoblasts proliferation and invasion was inhibited by KDM5C overexpression and was enhanced by KDM5C knockdown. Interestingly, KDM5C knockdown promoted trophoblast invasion in villous explant culture system. RNA-seq and ChIP-seq analyses revealed that KDM5C exerts anti-proliferation and anti-invasion effect by directly modulating H3K4 methylation level to repress the expression of a number of key regulatory genes. We show that two of these genes, TGFβ2, RAGE, are essential for the proliferation and invasion of trophoblasts. Taken together, our results show that the KDM5C is regulator of trophoblast function during early pregnancy and indicated that KDM5C may be involved in the pathogenesis of RM. Next Generation Sequencing Facilitates Quantitative Analysis of HTR-8/SVneo cells transduced with control or KDM5C-expression vector, and HTR-8/SVneo cells transduced with NC or KDM5C shRNA-expression vector,

2022-12-16 | GSE141716 | GEO

The histone demethylase KDM5C represses trophoblast proliferation and invasion in woman with recurrent miscarriage [ChIP-seq]

Project description:KDM5C is a H3K4- specific demethylase, which has multiple biological roles in development and disease. However, the role of KDM5C in trophoblasts at the maternal-fetal interface remains unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from patient with recurrent miscarriage (RM). Trophoblasts proliferation and invasion was inhibited by KDM5C overexpression and was enhanced by KDM5C knockdown. Interestingly, KDM5C knockdown promoted trophoblast invasion in villous explant culture system. RNA-seq and ChIP-seq analyses revealed that KDM5C exerts anti-proliferation and anti-invasion effect by directly modulating H3K4 methylation level to repress the expression of a number of key regulatory genes. We show that two of these genes, TGFβ2, RAGE, are essential for the proliferation and invasion of trophoblasts. Taken together, our results show that the KDM5C is regulator of trophoblast function during early pregnancy and indicated that KDM5C may be involved in the pathogenesis of RM. To characterize genome-wide H3K4me3 chromatin-state of HTR-8/SVneo cells.

2022-12-16 | GSE141717 | GEO

The histone demethylase KDM5C represses trophoblast proliferation and invasion in woman with recurrent miscarriage

Project description:KDM5C is a histone H3K4-specific demethylase, which has been shown to play a key role in biological disease and development. However, the role of KDM5C in trophoblasts at early pregnancy is currently unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from recurrent miscarriage (RM) patients compared with healthy controls (HCs). Trophoblast proliferation and invasion was inhibited by KDM5C overexpression and was promoted by KDM5C knockdown. Transcriptome sequencing revealed that elevated KDM5C exerted anti-proliferation and anti-invasion effects by repressing the expression of essential regulatory genes. The combination analysis of RNA-seq, ChIP-seq and CUT&Tag assay showed that KDM5C overexpression leads to the reduction of H3K4me3 on the promoters and the corresponding downregulation of expression of several regulatory genes in trophoblasts. Among these genes, TGFβ2 and RAGE are essential for the proliferation and invasion of trophoblasts. Importantly, overexpression of KDM5C by a systemically delivered KDM5C adenovirus vector (Ad-KDM5C) promoted embryo resorption rate in mouse. Our results support that KDM5C is an important regulator of the trophoblast function during early pregnancy, and suggesting that KDM5C activity could be responsible for epigenetic alterations seen RM disease. This SuperSeries is composed of the SubSeries listed below.

2022-12-16 | GSE141718 | GEO

The Kdm5c histone demethylase controls enhancer and promoter function.

Project description:Here, we show that the Kdm5c/Smcx member of the Jarid1 family of H3K4 demethylases is recruited to both enhancer and core promoter elements in ES and neuronal progenitor cells (NPC). Knockdown of Kdm5c deregulates transcription via a local increase in H3K4me3. While at core promoters the function of Kdm5c is to restrict transcription, loss of Kdm5c impairs enhancer function. Remarkably, an impaired enhancer function activates promoter activity from Kdm5c-bound intergenic regions. Our results demonstrate that the Kdm5c demethylase plays a crucial role in the functional identity and discrimination of enhancers and core promoters. We speculate that this is related to recruitment of H3K4me3 binders like the TFIID and NURF complexes6-8. Providing functional identity to genomic regions through balancing enzymes that deposit and remove histone modifications may prove to be a general epigenetic mechanism for the functional indexing of eukaryotic genomes. Examination of the KDM5C binding sites in mouse embryonic stem cells and in neuronal progenitor cells. Effect of KDM5C knock down on H3K4me3 and H3K4me1 levels and gene expression.

2013-04-01 | E-GEOD-34975 | biostudies-arrayexpress

The Kdm5c histone demethylase controls enhancer and promoter function.

2013-04-01 | GSE34975 | GEO

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Project description:The goal of this study is to compare miRNAs expressed by EGF treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during EGF-mediated HTR-8/SVneo cell invasion

2019-01-04 | GSE124585 | GEO

Differential expression of miRNAs in HGF treated HTR-8/SVneo versus untreated control by next generation sequencing

Project description:The goal of this study is to compare miRNAs expressed by HGF treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during HGF-mediated HTR-8/SVneo cells invasion

2019-01-29 | GSE125767 | GEO

Differential expressed genes in EGF treated HTR-8/SVneo versus untreated control by next generation sequencing

Project description:The goal of this study is to compare mRNAs expressed by EGF treated HTR-8/SVneo cells to iRNAs expressed in untreated control HTR-8/SVneo cells to identify various genes which play a role during EGF-mediated HTR-8/SVneo cell invasion

2019-01-04 | GSE124586 | GEO

Differential expression of miRNAs in IFN-gamma treated HTR-8/SVneo versus untreated control by next generation sequencing

Project description:The goal of this study is to compare miRNAs expressed by IFN-gamma treated HTR-8/SVneo cells to miRNAs expressed in untreated control HTR-8/SVneo cells to identify micro RNAs which play a role during IFN-gamma-mediated HTR-8/SVneo cells invasion

2019-01-29 | GSE125774 | GEO

Differential expression of mRNAs in IFN-gamma treated HTR-8/SVneo versus untreated control by next generation sequencing

Project description:The goal of this study is to compare genes expressed by IFN-gamma treated HTR-8/SVneo cells to genes expressed in untreated control HTR-8/SVneo cells to identify genes which play a role during IFN-gamma-mediated HTR-8/SVneo cells invasion

2019-01-29 | GSE125778 | GEO

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