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Unraveling the role of human TSC-specific TFs [ChIP-Seq]

ABSTRACT: Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208361 | GEO | 2023/03/22

REPOSITORIES: GEO

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Unraveling the role of human TSC-specific TFs [RNA-Seq]

Project description:Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.

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Unraveling the role of human TSC-specific TFs

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Unraveling the role of human TSC-specific TFs [ChIP-Seq]

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Unraveling the role of human TSC-specific TFs [RNA-Seq]

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Super-enhancer-guided decoding of gene regulatory networks in trophoblast stem cells

Project description:Cells belonging to trophoblast lineage are required for proper implantation and placentation, as well as the vascular, hematopoietic, and immunological properties of the placenta, a crucial organ mediating dynamic interactions between maternal and fetal tissues. Defects in trophoblast lineage development can cause early pregnancy failure or other pregnancy-related disorders. Despite its pivotal roles, the placenta remains as one of the least studied organs. Until now, only a handful of trophoblast-specific transcription factors (TFs) have been characterized, and underlying regulatory mechanisms modulating trophoblast lineage development remain poorly understood. Here we explore trophoblast stem cell (TSC)-specific super-enhancers (SEs) and subsequently identify SE-associated factors enriched with previously known and many unknown TFs modulating trophoblast lineage development. By mapping direct targets of 28 TSC-specific TFs in TSCs, we construct highly intertwined transcriptional regulatory networks where TFs are co-regulated and linked with signaling pathways, and which function as cellular modules dedicated to trophoblast lineage development. Additionally, we reveal that TSC-specific TFs alter their target sites corresponding to the reshaped enhancers during TSC differentiation. These findings advance our understanding on placenta biology.

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Unraveling the role of human TSC-specific TFs

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

2023-03-22 | GSE208539 | GEO

Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (ChIP-seq)

Project description:The placenta is an organ with extraordinary phenotypic diversity in eutherian mammals. Recent evidence suggest that numerous human placental enhancers are evolved from lineage-specific insertions of endogenous retroviruses (ERVs), yet the transcription factors (TFs) underlying their regulation remain largely elusive. Here, by first focusing on MER41, a primate-specific ERV family previously linked to placenta and innate immunity, we uncover the binding motifs of multiple crucial trophoblast TFs (GATA2/3, MSX2, GRHL2) in addition to innate immuninty TFs STAT1 and IRF1. Integration of ChIP-Seq data confirms the binding of GATA2/3 and MSX2 on the majority of MER41-derived enhancers in human trophoblast stem cells (TSCs). Notably, the usb-family composition of MER41-derived enhancers that are active in human TSCs are distinct from those activated upon interferon stimulation, which is determined by the binding of trophoblast TFs. We further demonstrate that GATA2/3 and MSX2 have prevalent binding on numerous other ERV families – indicating their broad impact on ERV-derived placental enhancers. Functionally, the derepression of many syncytiotrophoblast genes after disruption of MSX2 is likely to be mediated by enhancers derived from ERVs – suggesting ERVs are also important for mediating transcriptional repression in human TSCs. Overall, this study characterized the prevalent binding of GATA2/3, MSX2 and their co-factors on ERV-derived enhancers in human TSCs and provided mechanistic insights into the importance of ERVs in human trophoblast regulatory network.

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Regulation of endogenous retrovirus-derived regulatory elements by GATA2/3 and MSX2 in human trophoblast stem cells (RNA-seq)

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Genome-wide maps of adipogenic TFs during brown preadipocyte differentiation

Project description:Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for the deposition of H3K4me1/2 on enhancers remain elusive. Furthermore, the functions of these methyltransferases on enhancers and associated cell-type-specific gene expression are poorly understood. Here, we identify MLL4 (KMT2D) as a major H3K4 mono- and di-methyltransferase in mammalian cells. Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of MLL4 dramatically decreases H3K4me1/2 and H3K27ac on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Finally, we provide evidence that lineage-determining TFs recruit and require MLL4 to establish enhancers critical for cell-type-specific gene expression. Together, these results identify MLL4 as an H3K4 mono-/di-methyltransferase required for enhancer activation during cell differentiation. ChIP-Seq analyses of adipogenic TF (C/EBPalpha, C/EBPbeta, and PPARgamma) and Pol II profiles at D0 (day 0) and D2 (day 2) of adipogenesis in WT (MLL3-/-) and MLL4 KO (MLL3-/-;MLL4-/-) brown preadipocytes.

2013-12-17 | E-GEOD-50416 | biostudies-arrayexpress

Gene expression profiling reveals a novel regulatory role for Sox21 in mouse trophoblast stem cell differentiation.

Project description:In this study we introduced Sox21 as a new regulator of trophoblast stem cell (TSC) differentiation. The transcriptome of different cell types were analyzed and compared to identify a TSC gene signature. In order to identify novel TSC specific genes, we performed genome-wide expression profiling of TSCs, embryonic stem cells, epiblast stem cells, and mouse embryo fibroblasts derived from mice of the same genetic background (129S1/SvImJ).

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