Histone Demethylases and Trophoblast Differentiation
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PROVIDER: PRJNA742443 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human trophoblast differentiation
| PRJNA717066 | ENA
Project description:Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and differentiation. However, the roles of histone demethylases and activating histone modifications such as methylation of histone 3 lysine 4 (H3K4me3/me2) in regulating TS cell expression programs, and in priming the epigenetic landscape for trophoblast differentiation, are largely unknown. Here, we demonstrate that the H3K4 demethylase, KDM5B, regulates the H3K4 methylome and expression landscapes of TS cells. Depletion of KDM5B resulted in downregulation of TS cell self-renewal genes and upregulation of trophoblast-lineage genes, which was accompanied by altered H3K4 methylation. Moreover, we found that KDM5B resets the H3K4 methylation landscape during differentiation in the absence of the external self-renewal signal, FGF4, by removing H3K4 methylation from promoters of self-renewal genes, and of genes whose expression is enriched in TS cells. Altogether, our data indicate an epigenetic role for KDM5B in regulating H3K4 methylation in TS cells and during trophoblast differentiation.
2018-06-14 | GSE111846 | GEO
Project description:Trophoblast stem (TS) cells derived from the trophectoderm (TE) of mammalian embryos have the ability to self-renew indefinitely or differentiate into fetal lineages of the placenta. Epigenetic control of gene expression plays an instrumental role in dictating the fate of TS cell self-renewal and differentiation. However, the roles of histone demethylases and activating histone modifications such as methylation of histone 3 lysine 4 (H3K4me3/me2) in regulating TS cell expression programs, and in priming the epigenetic landscape for trophoblast differentiation, are largely unknown. Here, we demonstrate that the H3K4 demethylase, KDM5B, regulates the H3K4 methylome and expression landscapes of TS cells. Depletion of KDM5B resulted in downregulation of TS cell self-renewal genes and upregulation of trophoblast-lineage genes, which was accompanied by altered H3K4 methylation. Moreover, we found that KDM5B resets the H3K4 methylation landscape during differentiation in the absence of the external self-renewal signal, FGF4, by removing H3K4 methylation from promoters of self-renewal genes, and of genes whose expression is enriched in TS cells. Altogether, our data indicate an epigenetic role for KDM5B in regulating H3K4 methylation in TS cells and during trophoblast differentiation.
2018-06-14 | GSE111847 | GEO
Project description:The placenta serves as an essential organ for nurturing fetal growth throughout pregnancy. Histone modification is a crucial regulatory mechanism involved in numerous biological processes and development. Nevertheless, there remains a significant gap in our understanding regarding the precise mechanisms and extent to which various histone modifications influence the critical process of trophoblast lineage differentiation, which is fundamental to placental development. Here, we conducted a comprehensive mapping of H3K4me3, H3K27me3, H3K9me3, and H3K27ac loci during trophoblast stem cells (TSC) differentiation into syncytiotrophoblasts (ST) and extravillous trophoblasts (EVT) to investigate the regulatory roles and dynamic changes in histone modifications in trophoblast lineage specification.
2024-02-28 | GSE243059 | GEO
Project description:Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation. In this work, we employed static and stable isotope tracing untargeted metabolomics methods together with gene expression and histone acetylation studies in an established cell culture model of trophoblast differentiation. Trophoblast differentiation was associated with increased abundance of the TCA cycle intermediates citrate and α-ketoglutarate. Citrate was preferentially exported from mitochondria in the undifferentiated state but was retained to a larger extent within mitochondria upon differentiation. Correspondingly, differentiation was associated with decreased expression of the mitochondrial citrate transporter (CIC). CRISPR/Cas9 disruption of the mitochondrial citrate carrier showed that CIC is required for biochemical differentiation of trophoblast. Loss of CIC resulted in broad alterations in gene expression and histone acetylation. These gene expression changes were partially rescued through acetate supplementation. Taken together, these results highlight a central role for mitochondrial citrate metabolism in the orchestration of histone acetylation and gene expression during trophoblast differentiation.
2023-05-05 | GSE223514 | GEO
Project description:Increased RNA polymerase II binding to promoters of a subset of genes during trophoblast differentiation was closely correlated with active histone marks.
2019-07-31 | GSE127288 | GEO
Project description:This dataset profiles the proteomic effects of altering BAP1 expression in human trophoblast stem cells and trophoblast organoids. Samples from control, BAP1-overexpressing, and BAP1-knockdown conditions were analyzed by LC–MS/MS. DIA-NN–based quantification and differential analysis revealed BAP1-dependent changes affecting trophoblast differentiation, inflammatory signaling, and pathways linked to early-onset preeclampsia.
2026-03-24 | PXD071497 | Pride
Project description:We investigate the relationship between histone succinylation and Jumonji C (JmjC) domain-containing histone demethylases, a class of enzymes that catalyzes the removal of histone methylation. By using quantitative proteomics and peptide pull-down assays, we identified Jumonji demethylases as candidate interactors of succinylated histone peptides. Biochemical assays demonstrate that succinylated histone peptides bind and inhibit the demethylase activity of KDM4D and KDM6B in a dose-dependent manner. Notably, these two demethylases are responsible for the removal of the silencing marks H3K9me2/3 and H3K27me2/3. We increased histone succinylation in a HepG2/C3A cell model by providing supraphysiological sodium succinate and demonstrated that H3K9me2/3 and H3K27me2/3 increased in relative abundance as well. CUT&Tag and ChIP–mass spectrometry revealed co-occurrence of succinylation with repressive methylation marks, together with reduced levels of transcribed RNA. Altogether, these findings support a model in which histone succinylation contributes to maintaining the silencing marks H3K9me2/3 and H3K27me2/3 on chromatin by locally inhibiting Jumonji domain demethylases. This work establishes a mechanistic link between metabolic state and chromatin regulation and suggests a role for histone succinylation in the maintenance of heterochromatin.
2026-05-22 | GSE331259 | GEO
Project description:While histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4+ T cell precursors. We show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Floxed alleles of the genes encoding Utx and Jmjd3 (Kdm6a and Kdm6b, respectively) were deleted in double positive (DP) thymocytes carrying a CD4 Cre transgene. Genome-wide H3K27Me3 ChipSeq was performed on (i) pre-selection (CD69lo) DP thymocytes from wild-type mice carrying an endogenous polyclonal TCR repertoire, (ii) mature (TCRhi CD24lo) CD4 SP thymocytes from wild type (Wt), Jmjd3KO, UtxKO and dKO mice carrying an endogenous polyclonal TCR repertoire and (iii) mature (Va2hi CD24lo) CD4 SP thymocytes from wild type and dKO mice carrying the OTII TCR transgene.
2015-09-02 | E-GEOD-70795 | biostudies-arrayexpress
Project description:While histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4+ T cell precursors. We show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress.
2015-09-02 | GSE70795 | GEO