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Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency

ABSTRACT: Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency

PROVIDER: PRJNA506240 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8216250.fastq.gz	Fastqsanger.gz
	SRR8216251.fastq.gz	Fastqsanger.gz
	SRR8210422_1.fastq.gz	Fastqsanger.gz
	SRR8210422_2.fastq.gz	Fastqsanger.gz
	SRR8216252.fastq.gz	Fastqsanger.gz

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Similar Datasets

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency.

Project description:Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long-range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state.

| S-EPMC9925822 | biostudies-literature

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [RNA-seq]

Project description:Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [RNA-seq]

| PRJNA506322 | ENA

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [DNA-seq]

Project description:Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [DNA-seq]

| PRJNA506235 | ENA

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [RNA-seq]

Project description:Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state.

2019-11-30 | GSE122753 | GEO

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency [DNA-seq]

Project description:Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state.

2019-11-30 | GSE122748 | GEO

Long range inter-chromosomal interaction of Oct4 distal enhancer loci regulates ESCs pluripotency

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

2019-11-30 | GSE122755 | GEO

OCT4 IP-MS in Naive and Primed Human ESCs

Project description:Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes.

2021-09-12 | PXD026556 | Pride

A balanced Oct4 protein interaction network is crucial for maintaining pluripotency

Project description:Oct4 is considered a master transcription factor for pluripotent cell self-renewal and embryo development. It primarily collaborates with other transcriptional factors or coregulators to maintain pluripotency. However, it is still unclear how Oct4 interacts with its partners. Here, we show that the Oct4 linker interface mediates competing and balanced Oct4 protein interactions which are crucial for maintaining pluripotency. Linker mutant ESCs maintain the key pluripotency genes expression, but show decreased expression of self-renewal genes and increased expression of differentiation genes which result in impaired ESCs self-renewal and early embryonic lethality. Linker mutation dose not affect Oct4 genomic binding and transactivation potential, but breaks the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 was decreased, but interactions between Oct4 and Cbx1, Ctr9, Cdc73 were increased which disrupt the epigenetic state of ESCs. Overexpression of Klf5 or knockdown Cbx1, Cdc73 rescue the cellular phenotype of linker mutant ESCs by rebalancing Oct4 interactome indicating that different partners interact with Oct4 competitively. Thus, by showing how Oct4 interacts with different partners, we provide novel molecular insights to explain how Oct4 contributes to the maintenance of pluripotency.

2021-12-10 | PXD017456 | Pride

ChIP Seq of Oct4, Nanog, H3K27me3 in Oct4+/+ and Oct4 +/- mES cells

Project description:Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centred on the transcription factors Oct4 and Nanog. ESCs fluctuate between states of high and low Nanog expression that direct efficient or inefficient self-renewal. To date, robust self-renewing ESC states have only been attained by chemical inhibition of signalling pathways or enforced transgene expression. Here we show that ESCs expressing a reduced range of Oct4 concentrations, typified by Oct4 heterozygous ESCs exhibit stable robust pluripotency. Despite this reduced Oct4 concentration range, this state is characterised by increased genome-wide binding of Oct4, particularly at pluripotency-associated enhancers, homogeneous expression of pluripotency transcription factors, enhanced self-renewal efficiency and delayed differentiation kinetics. In this state, ESCs exhibit increased wnt expression, enhanced LIF-sensitivity, non-responsiveness to FGF signalling and can clonally maintain pluripotency without BMP but remain dependent upon LIF. Robust pluripotency is destabilised either by alteration of the Oct4 level or by removal of LIF. Our findings suggest that robust pluripotency originates from cells with a reduced Oct4 protein concentration and that the wild-type Oct4 range enables effective differentiation.

2013-05-07 | E-MTAB-1617 | biostudies-arrayexpress

Endogenous OCT4 interactome in hESC

Project description:In two widely-cited OCT4-protein interactome papers, Ding et al. (Ding et al., 2012) used murine ESC nuclear extract to identify OCT4 interactome in nucleus and Pardo et al. (Pardo et al., 2010) used whole cell lysate to identify OCT4 interactome in murine ESCs. In both papers, Benzonase, a genetically engineered endonuclease was employed to fragment genome DNA which significantly improved the enrichment efficiency of nuclear TFs. Since our focus was on cytosolic pool of OCT4, we used mild conditions for cell lysis and modified the Pardo’s method by omitting the addition of any nucleases to the lysis buffer. Such conditions not only retained the protein/RNA interactions, but also enabled precipitation of the nuclear TFs with genome DNA, and hence a relative enrichment of the cytosolic proteins and other soluble nuclear proteins (such as splicing factors) in the supernatant, and therefore allowed us to minimize the interference of the TF roles of OCT4 and to focus more on its novel RBP roles.

2025-05-06 | PXD033840 | Pride

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