ChIP-Seq of Histone Modifications in 3iL Human Embryonic Stem Cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Jonathan Goke
PROVIDER: E-MTAB-2041 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Human embryonic stem cells (hESCs) are isolated from the inner cell mass of the blastocysts. The pluripotent properties of hESCs enable the derivation of cell-types or tissues of different lineages for potential applications such as therapeutics discovery and regenerative medicine. Even though hESCs are pluripotent, differences have been observed when compared to the native pluripotent epiblast cells of the blastocyst. We use a chemical approach (3iL: 3 small molecule inhibitor and cytokine) to induce an expression signature that more closely resembles native pluripotent cells. This experiment is STAT3 binding data in 3iL hESCs.
2013-12-05 | E-MTAB-2042 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) are isolated from the inner cell mass of the blastocysts. The pluripotent properties of hESCs enable the derivation of cell-types or tissues of different lineages for potential applications such as therapeutics discovery and regenerative medicine. Even though hESCs are pluripotent, differences have been observed when compared to the native pluripotent epiblast cells of the blastocyst. We use a chemical approach (3iL: 3 small molecule inhibitor and cytokine) to induce an expression signature that more closely resembles native pluripotent cells. This experiment is the transcription factor binding data of the study.
2013-12-05 | E-MTAB-2044 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) are isolated from the inner cell mass of the blastocysts. The pluripotent properties of hESCs enable the derivation of cell-types or tissues of different lineages for potential applications such as therapeutics discovery and regenerative medicine. Even though hESCs are pluripotent, differences have been observed when compared to the native pluripotent epiblast cells of the blastocyst. We use a chemical approach (3iL: 3 small molecule inhibitor and cytokine) to induce an expression signature that more closely resembles native pluripotent cells. To better understand the difference between this hESC state and the conventional hESC state, we generated the global expression profiles using RNA-seq.
2014-12-12 | E-MTAB-2031 | biostudies-arrayexpress
Project description:The ERK/MAPK signal transduction cascade is one of the key pathways regulating proliferation and differentiation in development and disease. In human embryonic stem cells (hESCs), ERK signaling is required for their self-renewing property. Here we studied the convergence of the ERK signaling cascade at the DNA by mapping genome-wide kinase-chromatin interactions for ERK2 in hESCs. We observe that ERK2 targets genes coding for small RNAs, histones, and genes involved in cellular metabolism and cell cycle. We find that the transcription factor ELK1 is essential in hESCs and that ERK2 co-occupies promoters bound by ELK1. Strikingly, promoters bound by ELK1 without ERK2 are occupied by Polycomb group proteins that repress genes involved in lineage commitment. In summary, we propose a model where extracellular signaling-stimulated proliferation and intrinsic repression of differentiation is integrated to maintain the identity of hESCs.
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Project description:An experiment was performed to map the global binding profile of EZH2 in human embryonic stem cells (hESCs). How the Polycomb Repressive Complex 2 (PRC2) is recruited to the DNA in hESC remains largely unknown. Previous studies on the transcription factor PRDM14 suggested that PRDM14 plays a repressive role in hESCs. Here, we mapped the global binding profile of EZH2 in hESC to investigate the association of PRDM14 binding with the PRC2 in hESCs. EZH2 binding is found to be enriched in PRDM14 binding sites. The PRC2 dependent repressive role of PRDM14 is further supported by the strong correlation of PRDM14 binding with the repressive histone modification H3K27me3.
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Project description:Cellular metabolism and chromatin landscape both contribute to cell fate determination. However, their interplay remains poorly understood. Here we show that Prohibitin (PHB), an evolutionarily conserved protein, involves in a histone variant H3.3 chaperon HIRA complex-dependent epigenetic and metabolic circuitry to maintain the identity of human embryonic stem cells (hESCs). We found that silencing of PHB triggers hESC differentiation with concomitant enhancements of histone 3 (H3) lysine (K) methyl modifications as a result of the reduced production of α-ketoglutarate (α-KG), a metabolite required for activities of many dioxygenase and in turn chromatin structure1,2. Mechanistically, PHB acts as a functional member of the HIRA complex3,4. Resembling PHB deficiency, loss of HIRA in hESCs leads to massive differentiation and aberrant histone modifications, although it was previously found not to disrupt the self-renewal in mouse ESCs (mESCs)5. Genome-wide H3.3 ChIP- sequence analyses indicate that reduction of H3.3 deposition caused by PHB knock down is extremely similar to that induced by HIRA knock down. Specifically, silencing either HIRA or PHB leads to repressive chromatin characters at promoters of pluripotency genes and isocitrate dehydrogenases (IDHs), the enzyme responsible for α-KG production, but active chromatin features at promoters of developmental genes, paralleling to transcript levels of these genes. Our results identify PHB as an essential factor not only for hESC self-renewal but also for the proper function of the HIRA complex, linking the HIRA complex-dependent H3.3 deposition to the production of a critical metabolite required for shaping chromatin structure, and demonstrating the importance of the interplay between epigenetic state and metabolic regulation in cell fate determination. Examination of H3.3 deposition in NT, PHB, and HIRA siRNA treated hESCs respectively.
2016-08-11 | E-GEOD-72143 | biostudies-arrayexpress
Project description:Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells. Identification of p53 binding sites in hESC under three conditions: Pluripotent, DNA damaged, Differentiating
2013-10-18 | E-GEOD-39762 | biostudies-arrayexpress
Project description:Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells. Identification of p53 binding sites in hESC under three conditions : Pluripotent, DNA damaged, Differentiating
2013-10-18 | E-GEOD-39912 | biostudies-arrayexpress
Project description:Human embryonic stem cells (hESCs) harbor the ability to undergo lineage-specific differentiation into clinically relevant cell types. Transcription factors and epigenetic modifiers are known to play important roles in the maintenance of pluripotency of hESCs. However, little is known about regulation of pluripotency through splicing. In this study, we identify the spliceosome-associated factor SON as a novel factor essential for the maintenance of hESCs. Depletion of SON in hESCs results in the loss of pluripotency and cell death. Using genome-wide RNA profiling, we identified transcripts that are regulated by SON. Importantly, we confirmed that SON regulates the proper splicing of transcripts encoding for pluripotency regulators such as PRDM14, OCT4, E4F1 and MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In summary, we connect a splicing-regulatory network for accurate transcription production to the maintenance of pluripotency and self-renewal of hESCs.
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