Role of OCT4 as a transcription factor in pluripotent stem cells [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA1188605 | ENA |
REPOSITORIES: ENA
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Project description:Pluripotent stem cells (PSCs), known for their unlimited ability to self-renew and differentiate into all three germ layers, have emerged as a promising cell source for regenerative therapies aimed at treating various diseases and injuries.OCT4 is a key pluripotent marker and transcription factor in PSCs, which regulates numerous biological processes of PSCs. This data demonstrates the potential role of OCT4 as a transcription factor.
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Project description:The nucleosome is a fundamental unit of chromatin in eukaryotes, and generally prevents the binding of transcription factors to genomic DNA. Pioneer transcription factors overcome the nucleosome barrier, and bind their target DNA sequences in chromatin. OCT4 is a representative pioneer transcription factor that plays a role in stem cell pluripotency. In the present study, we biochemically analyzed the nucleosome binding by OCT4. Crosslinking mass spectrometry showed that OCT4 binds the nucleosome.
2020-05-13 | PXD019160 | JPOST Repository
Project description:Pluripotency can be induced in murine and human fibroblast by transduction of four transcription factors (Oct4, Sox2, Klf4 and c-Myc). Previously we reported that two factors (Oct4 and Klf4) are sufficient for reprogramming adult mouse neural stem cells (NSCs) to a pluripotent state. However, although NSCs endogenously express the factors Sox2, c-Myc, and Klf4, our previous report does not elucidate why exogenous expression of either Klf4 or c-Myc is still required for reprogramming. Here we report that exogenous expression of Oct4 is sufficient to generate one-factor induced pluripotent stem (1F iPS) cells without any oncogenic factors, such as c-Myc and Klf4, from mouse adult NSCs, which endogenously express Sox2, c-Myc, and Klf4, and also intermediate reprogramming markers alkaline phosphatase (AP), stage-specific embryonic antigen-1 (SSEA-1). These results extend our previous report proposing that somatic cells can be reprogrammed to a pluripotent state with a reducing number of reprogramming factors when the complementing factors are endogenously expressed in the somatic cells. Experiment Overall Design: 10 hybridizations in total. Experiment Overall Design: NSC-derived iPS cells by one-factor (Oct4) in triplicate: Experiment Overall Design: - NSC_1F_iPS_1 Experiment Overall Design: - NSC_1F_iPS_2 Experiment Overall Design: - NSC_1F_iPS_3 Experiment Overall Design: One-factor (Oct4) iPS cell-derived NSC in triplicate: Experiment Overall Design: - 1F_iPS_NSC_1 Experiment Overall Design: - 1F_iPS_NSC_2 Experiment Overall Design: - 1F_iPS_NSC_3 Experiment Overall Design: Neural stem cell (NSC) derived from brain of OG2/Rosa26 mice: Experiment Overall Design: - NSC_1 Experiment Overall Design: - NSC_2 Experiment Overall Design: - NSC_3 Experiment Overall Design: - NSC_4
2009-02-08 | E-GEOD-12499 | biostudies-arrayexpress
Project description:Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). We mapped the protein-protein interactions of OCT4 in naive and primed hESCs, revealing extensive connections to ATP-dependent nucleosome remodeling complexes. In naive hESCs, OCT4 is associated with both BRG1 and BRM, the two mutually exclusive ATPase subunits of the BAF complex. Genome-wide location analyses and genetic deletion studies reveal that these two enzymes exert a functionally redundant role in transcriptional regulation of blastocyst-specific genes. In contrast, OCT4 cooperates with BRG1 and the transcription factor SOX2 to create an open chromatin architecture at neural lineage-associated genes in primed hESCs. This work offers insight into the regulation of human stem cell identity and reveals how a common transcription factor utilizes differential compositions of the BAF complex in controlling distinct transcriptional programs governing naive vs. primed human pluripotent states.
2021-07-01 | GSE147716 | GEO
Project description:Resolution of early molecular events preceding endogenous OCT4 activation is critical to understanding the mechanism of reprogramming somatic cells to induced pluripotent stem cells (iPSCs), yet capturing transient regulators at the onset of reprogramming is difficult in heterogeneous populations of asynchronously reprogramming fibroblasts following four-factor transduction. To address this need, we used a heterokaryon system to identify an early and transiently expressed homeobox transcription factor, NKX3-1. Upon knockdown of NKX3-1, iPSC reprogramming is abrogated. Further, we identify that NKX3-1 functions downstream of the IL6-STAT3 regulatory network to activate endogenous OCT4. Importantly, we show that NKX3-1 can substitute for exogenous OCT4 to reprogram both mouse and human fibroblasts at comparable efficiencies generate fully pluripotent stem cells. Our findings establish an essential role for NKX3-1, previously known as a prostate-specific tumor suppressor, in iPSC reprogramming.
2019-05-13 | GSE103535 | GEO
Project description:Resolution of early molecular events preceding endogenous OCT4 activation is critical to understanding the mechanism of reprogramming somatic cells to induced pluripotent stem cells (iPSCs), yet capturing transient regulators at the onset of reprogramming is difficult in heterogeneous populations of asynchronously reprogramming fibroblasts following four-factor transduction. To address this need, we used a heterokaryon system to identify an early and transiently expressed homeobox transcription factor, NKX3-1. Upon knockdown of NKX3-1, iPSC reprogramming is abrogated. Further, we identify that NKX3-1 functions downstream of the IL6-STAT3 regulatory network to activate endogenous OCT4. Importantly, we show that NKX3-1 can substitute for exogenous OCT4 to reprogram both mouse and human fibroblasts at comparable efficiencies generate fully pluripotent stem cells. Our findings establish an essential role for NKX3-1, previously known as a prostate-specific tumor suppressor, in iPSC reprogramming.
2019-05-13 | GSE103509 | GEO
Project description:The pluripotency factor Oct4 is essential for the maintenance of naïve pluripotent stem cells in vitro and in vivo. However, the specific role of Oct4 in this process remains unknown. Here, we developed a rapid protein-level Oct4 depletion system that demonstrates that the immediate downstream response to loss of Oct4 is reduced expression of key pluripotency factors. Our data show a requirement for Oct4 for the efficient transcription of several key pluripotency factors, and suggest that expression of trophectoderm markers is a subsequent event. Additionally, we find that Nanog is competent to bind to the genome in the absence of Oct4, and this binding is in fact enhanced. Globally, however, active enhancer associated histone mark H3K27ac is depleted. Our work establishes that while Oct4 is required for the maintenance of the naïve transcription factor network, at a normal ESC level it antagonises this network through inhibition of Nanog binding
2021-06-17 | GSE168575 | GEO
Project description:The pluripotency factor Oct4 is essential for the maintenance of naïve pluripotent stem cells in vitro and in vivo. However, the specific role of Oct4 in this process remains unknown. Here, we developed a rapid protein-level Oct4 depletion system that demonstrates that the immediate downstream response to loss of Oct4 is reduced expression of key pluripotency factors. Our data show a requirement for Oct4 for the efficient transcription of several key pluripotency factors, and suggest that expression of trophectoderm markers is a subsequent event. Additionally, we find that Nanog is competent to bind to the genome in the absence of Oct4, and this binding is in fact enhanced. Globally, however, active enhancer associated histone mark H3K27ac is depleted. Our work establishes that while Oct4 is required for the maintenance of the naïve transcription factor network, at a normal ESC level it antagonises this network through inhibition of Nanog binding
2021-06-17 | GSE168576 | GEO
Project description:The mechanisms whereby the crucial pluripotency transcription factor Oct4 regulates target gene expression are incompletely understood. Using an assay system based on partially differentiated embryonic stem cells, we show that Oct4 opposes accumulation of local H3K9me2, and subsequent Dnmt3a-mediated DNA methylation. Upon binding DNA, Oct4 recruits the histone lysine demethylase Jmjd1c. ChIP timecourse experiments identify a stepwise Oct4 mechanism involving Jmjd1c recruitment and H3K9me2 demethylation, transient FACT complex recruitment, and nucleosome depletion. Genome-wide and targeted ChIP confirms binding of newly-synthesized Oct4, together with Jmjd1c and FACT, to the Pou5f1 enhancer and a small number of other Oct4 targets, including the Nanog promoter. Histone demethylation is required for both FACT recruitment and H3 depletion. Jmjd1c is required to induce endogenous Oct4 expression and fully reprogram fibroblasts to pluripotency, indicating that the assay system identifies functional Oct4 cofactors. These findings indicate that Oct4 sequentially recruits activities that catalyze histone demethylation and depletion.
2015-01-23 | GSE65192 | GEO
Project description:Replacing the transcription factor OCT4, one of the master pluripotency regulators, by small molecules has been a long standing challenge to establish small molecule based reprogramming for the generation of human chemically induced pluripotent stem cells (hciPSCs). Using a cell-based high throughput screen, we have previously identified a new series of OCT4-inducing compounds (O4Is). In this paper, we prepared metabolically stable analogues, including O4I4, which strongly activate pluripotency-associated signaling. In combination with a transcription factor cocktail of SOX2, KLF4, MYC, and LIN28 (collectively referred to as CSKML) we achieved to reprogram human fibroblasts into a stable and authentic pluripotent state independent of exogenous OCT4. Transcriptomic analysis of fibroblasts reprogrammed by this approach revealed that O4I4 activated bone morphogenetic protein (BMP)/SMAD/ID signaling at the early stage of reprogramming and subsequent expression of the chromatin modifier, high mobility group A1 (HMGA1), resulting in re-activation of endogenous OCT4 to initiate the reprogramming process. Consistently, chemical or genetic inhibition of BMP/SMAD/ID or HMGA1 was found to block cellular reprogramming. In C.elegans and Drosophila, O4I4 expanded life spans in a BMP-signaling pathway-dependent manner. Given limitations of OCT4-based reprogramming, our findings provide an alternative to OSKM-mediated iPSC generation, and importantly unravel previously-unrecognized molecular mechanisms of pluripotency in the context of regenerative medicine and rejuvenation therapy.
2022-04-06 | GSE200136 | GEO