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Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [ChIP-Seq]

ABSTRACT: Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination.

ORGANISM(S): Mus musculus

PROVIDER: GSE66735 | GEO | 2015/05/07

SECONDARY ACCESSION(S): PRJNA277842

REPOSITORIES: GEO

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Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [ChIP-Seq]

Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. Genome binding/occupancy profiling of Tex10 was performed in mouse embryonic stem cells by ChIP sequencing.

2015-05-07 | E-GEOD-66735 | biostudies-arrayexpress

Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [RNA-Seq]

Project description:Super-enhancers (SEs) are large clusters of transcriptional enhancers that are co-occupied by multiple lineage specific transcription factors driving expression of genes that define cell identity. In embryonic stem cells (ESCs), SEs are highly enriched for Oct4, Sox2, and Nanog in the enhanceosome assembly and express enhancer RNAs (eRNAs). We sought to dissect the molecular control mechanism of SE activity and eRNA transcription for pluripotency and reprogramming. Starting from a protein interaction network surrounding Sox2, a key pluripotency and reprogramming factor that guides the ESC-specific enhanceosome assembly and orchestrates the hierarchical transcriptional activation during the final stage of reprogramming, we discovered Tex10 as a novel pluripotency factor that is evolutionally conserved and functionally significant in ESC self-renewal, early embryo development, and reprogramming. Tex10 is enriched at SEs in a Sox2-dependent manner and coordinates histone acetylation and DNA demethylation of SEs. Our study sheds new light on epigenetic control of SE activity for cell fate determination. RNA sequencing analysis was performed in mouse embryonic stem cells with Luciferase and Tex10 knockdown. RNA-seq Experiments were carry out in two biological replicates.

2015-05-07 | E-GEOD-66734 | biostudies-arrayexpress

Tex10 Coordinates Epigenetic Control of Super-Enhancer Activity for Pluripotency and Reprogramming [RNA-Seq]

2015-05-07 | GSE66734 | GEO

Tex10 in spermatogenesis

Project description:Conditional Tex10 knockout compromises the spermatogenesis

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Induction of pluripotency in mouse somatic cells with lineage specifiers (RNA-seq)

Project description:For years, reprogramming factors that induce pluripotency have been identified primarily from ESC-enriched factors, pluripotency-associated factors such as Oct4, Sox2, Klf4, c-Myc, Nanog, Esrrb, Sall4, Utf1, Lin28, PRDM14, and Tet2. Through genome-wide screen we identified novel regulators of reprogramming. Our study is the first proof-of-principle report to suggest a putative general "seesaw model". This model provides novel mechanistic insight into the fundamental understanding of the establishment of cellular identity during programming and reprogramming. Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc.

2013-05-28 | E-GEOD-47442 | biostudies-arrayexpress

Induction of pluripotency in mouse somatic cells with novel factors (expression)

Project description:For years, reprogramming factors that induce pluripotency have been identified primarily from ESC-enriched factors, pluripotency-associated factors such as Oct4, Sox2, Klf4, c-Myc, Nanog, Esrrb, Sall4, Utf1, Lin28, PRDM14, and Tet2. Through genome-wide screen we identified novel regulators of reprogramming. Our study is the first proof-of-principle report to suggest a putative general mathematical model. This model provides novel mechanistic insight into the fundamental understanding of the establishment of cellular identity during programming and reprogramming. Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc Through genome-wide screen to identify novel factors of reprogramming in addition to Oct4, Sox2, Klf4, cMyc. Induced pluripotent stem cells versus mouse embryonic fibroblast.

2013-05-28 | E-GEOD-47441 | biostudies-arrayexpress

RNAi Screening Identifies that TEX10 Promotes the Proliferation of Colorectal Cancer Cells by Increasing NF-κB Activation

Project description:Colorectal cancer (CRC) has become a predominant cancer worldwide. In order to understand the process of carcinogenesis, an shRNA library screening is employed for searching candidate genes that promote proliferation in the CRC cell line HT29. The candidate genes overlapped with differentially expressed genes in 32 CRC tumor tissues in the GEO dataset GSE8671. The seventh-ranked TEX10 is upregulated in CRC and its knockdown decreased cell proliferation. The TEX10 high-expression group exhibits worse overall survival (P = 0.003) and progression-free survival (P < 0.001) than the TEX10 low-expression group. TEX10 depletion decreases the growth of CRC cells in vitro and in vivo. GSEA indicates that the NF-κB pathway is significantly enriched in the genes downregulated by TEX10 knockdown. Mechanistically, TEX10 interacts with p65 and increases its nuclear localization. TEX10 promotes p65 occupancy at gene promoters and regulates the expression of a subset of p65-targeted genes including TNFAIP8, SAT1 and IL6ST. Taken together, this study identifies that TEX10 promotes the proliferation of CRC cells in a p65-dependent manner. In addition, high TEX10 expression is associated with poor prognosis in CRC patients.

2020-10-05 | GSE147334 | GEO

Tex10 in primordial gem cell-like cell (PGCLC) specification and spermatogenesis

Project description:Tex10 depletion compromises the PGCLC specification and spermatogenesis

2023-06-14 | GSE180800 | GEO

SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells [array]

Project description:The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc modification, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor.

2016-03-07 | GSE69593 | GEO

SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells[ChIP-seq]

2016-03-07 | GSE69592 | GEO