Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA172728 | ENA |
REPOSITORIES: ENA
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Project description:A small number of transcription factors, including Oct-3/4 and Sox2, constitute the transcriptional network that maintains pluripotency in embryonic stem (ES) cells. Previous reports suggested that some of these factors form a complex that binds the Oct-Sox element, a composite sequence consisting of closely juxtaposed Oct-3/4-binding and Sox2-binding sites. However, little is known regarding the components of the complex. In this study, we show that Sall4, a member of the Spalt-like family of proteins, directly interacts with Sox2 and Oct-3/4. Sall4 in combination with Sox2 or Oct-3/4 simultaneously occupies the Oct-Sox elements in mouse ES cells. Sall4 knockdown led to differentiation of ES cells. Overexpression of Sall4 in ES cells increased reporter activities in a luciferase assay when the Pou5f1- or Nanog-derived Oct-Sox element was included in the reporter. Microarray analyses revealed that Sall4 and Sox2 bound to the same genes in ES cells significantly more frequently than expected from random coincidence. These factors appeared to bind the promoter regions of a subset of the Sall4- and Sox2-double-positive genes in precisely similar distribution patterns along the promoter regions, suggesting that Sall4 and Sox2 associate with such Sall4/Sox2-overlapping genes as a complex. Importantly, gene ontology analyses indicated that the Sall4/Sox2-overlapping gene set is enriched for genes involved in maintaining pluripotency. Sall4/Sox2/Oct-3/4-triple-positive genes identified by referring to a previous study identifying Oct-3/4-bound genes in ES cells were further enriched for pluripotency genes than Sall4/Sox2-double-positive genes. These results demonstrate that Sall4 contributes to the transcriptional network operating in pluripotent cells, together with Oct-3/4 and Sox2. ChIP-on-chip experiments using anti-Sall4 or anti-Sox2 antibody were performed.
2012-12-28 | E-GEOD-40072 | biostudies-arrayexpress
Project description:A small number of transcription factors, including Oct-3/4 and Sox2, constitute the transcriptional network that maintains pluripotency in embryonic stem (ES) cells. Previous reports suggested that some of these factors form a complex that binds the Oct-Sox element, a composite sequence consisting of closely juxtaposed Oct-3/4-binding and Sox2-binding sites. However, little is known regarding the components of the complex. In this study, we show that Sall4, a member of the Spalt-like family of proteins, directly interacts with Sox2 and Oct-3/4. Sall4 in combination with Sox2 or Oct-3/4 simultaneously occupies the Oct-Sox elements in mouse ES cells. Sall4 knockdown led to differentiation of ES cells. Overexpression of Sall4 in ES cells increased reporter activities in a luciferase assay when the Pou5f1- or Nanog-derived Oct-Sox element was included in the reporter. Microarray analyses revealed that Sall4 and Sox2 bound to the same genes in ES cells significantly more frequently than expected from random coincidence. These factors appeared to bind the promoter regions of a subset of the Sall4- and Sox2-double-positive genes in precisely similar distribution patterns along the promoter regions, suggesting that Sall4 and Sox2 associate with such Sall4/Sox2-overlapping genes as a complex. Importantly, gene ontology analyses indicated that the Sall4/Sox2-overlapping gene set is enriched for genes involved in maintaining pluripotency. Sall4/Sox2/Oct-3/4-triple-positive genes identified by referring to a previous study identifying Oct-3/4-bound genes in ES cells were further enriched for pluripotency genes than Sall4/Sox2-double-positive genes. These results demonstrate that Sall4 contributes to the transcriptional network operating in pluripotent cells, together with Oct-3/4 and Sox2.
2012-12-28 | GSE40072 | GEO
Project description:Embryonic stem cell (ESCs) identity is orchestrated by co-operativity between the transcription factors (TFs) Sox2 and the class V POU-TF, Oct4 at composite Sox/Oct motifs. Neural stem cells (NSCs) lack Oct4 but express Sox2 and class III POU-TFs. This raises the question of how Sox2 interacts with POU-TFs to transcriptionally specify ESCs or NSCs. Here we show that Oct4 alone binds the Sox/Oct motif and the octamer-containing palindromic MORE equally well. Sox2 binding selectively increases the affinity of Oct4 for the Sox/Oct motif. In contrast, Oct6 binds preferentially to the MORE, and is unaffected by Sox2. ChIP-seq in NSCs shows the MORE to be the most enriched motif for class III POU-TFs, with MORE sub-types apparent, but no Sox/Oct motif enrichment. These results suggest that in NSCs, co-operativity between Sox2 and class III POU-TFs may not occur and that POU-TF driven transcription uses predominantly the MORE cis architecture. Thus, distinct interactions between Sox2 and POU-TF subclasses distinguish pluripotent ESCs from multipotent NSCs, providing molecular insight into how Oct4 alone can convert NSCs to pluripotency.
2015-08-21 | GSE69859 | GEO
Project description:We show here by using genome-wide ChIP-sequencing that lineage segregation involves multiple Sox/Oct partnership. In undifferentiated ES cells Oct4 interacts with Sox2 and both TFs bind on the 'canonical' motif, whereas in cells commited to PrE lineage Oct4 switches from Sox2 to Sox17 interaction and this complex bind to a unique "compressed" motif. ChIP-sequencing has been done for Sox2, Sox17 and Oct4 in the pluripotent context or PrE context
2013-04-23 | E-GEOD-43275 | biostudies-arrayexpress
Project description:We show here by using genome-wide ChIP-sequencing that lineage segregation involves multiple Sox/Oct partnership. In undifferentiated ES cells Oct4 interacts with Sox2 and both TFs bind on the 'canonical' motif, whereas in cells commited to PrE lineage Oct4 switches from Sox2 to Sox17 interaction and this complex bind to a unique "compressed" motif.
2013-04-23 | GSE43275 | GEO
Project description:Pluripotent stem cells are a hallmark of animal multicellularity. Sox and POU family transcription factors are pivotal for stemness and were believed to be animal innovations as they were reported absent from the genomes of their unicellular relatives. Here we describe new unicellular holozoan orthologues to Sox and POU families, indicating that they emerged before the appearance of animals. We show that choanoflagellate and filasterean Sox genes have DNA binding specificity similar to Sox2. Choanoflagellate Sox can partner with the POU member Oct4 on DNA elements found in pluripotency enhancers. Consistently, choanoflagellate – but not filasterean – Sox genes can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSC). In contrast, choanoflagellate POU harbors a unique DNA-binding profile that differs from Oct4 and cannot generate iPSCs. Pluripotency reprogramming with reconstructed ancestral Sox genes shows that their molecular ability to induce stemness was already present in the last common ancestor of animals and their unicellular relatives. Our findings imply that the evolution of stem cells exploited a pre-existing set of transcription factors, where the critical innovation involved an initial change in DNA specificity of POU and the exaptation of the ancestral capacity to interact with Sox transcription factors.
2024-10-23 | GSE253887 | GEO
Project description:Pluripotent stem cells are a hallmark of animal multicellularity. Sox and POU family transcription factors are pivotal for stemness and were believed to be animal innovations as they were reported absent from the genomes of their unicellular relatives. Here we describe new unicellular holozoan orthologues to Sox and POU families, indicating that they emerged before the appearance of animals. We show that choanoflagellate and filasterean Sox genes have DNA binding specificity similar to Sox2. Choanoflagellate Sox can partner with the POU member Oct4 on DNA elements found in pluripotency enhancers. Consistently, choanoflagellate – but not filasterean – Sox genes can replace Sox2 to reprogram mouse somatic cells into induced pluripotent stem cells (iPSC). In contrast, choanoflagellate POU harbors a unique DNA-binding profile that differs from Oct4 and cannot generate iPSCs. Pluripotency reprogramming with reconstructed ancestral Sox genes shows that their molecular ability to induce stemness was already present in the last common ancestor of animals and their unicellular relatives. Our findings imply that the evolution of stem cells exploited a pre-existing set of transcription factors, where the critical innovation involved an initial change in DNA specificity of POU and the exaptation of the ancestral capacity to interact with Sox transcription factors.
2024-10-23 | GSE253886 | GEO
Project description:Stemness depends on a series of specific transcription regulators that suppress default differentiation and/or promote self-renewal. A prominent example thereof is SOX2 (SRY homology Box 2), a protein that further contributes to pluripotency and the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). Here we uncover that SOX2 exerts these functions not only via transcriptional roles, but also by directly regulating translation. We show that SOX2 associates with ribosomal 40S subunits in the cytoplasm to alter the protein expression of signaling factors and metabolic components pivotal for stemness. Specifically, a low complexity region in the C-terminal part of SOX2 that interacts with the ribosome to modulate protein synthesis, is identified as critically required for SOX2-induced clonogenicity in human cancer cells and the reprogramming of fibroblasts to iPSCs. Mechanistically, SOX2 translationally enforces insulin/PI3K signaling while suppressing the formation of acetyl CoA synthetase 2 (ACSS2) protein, a driver of acetate consuming cell differentiation. Expression of either full-length SOX2 or its C-terminus only increases glucose consumption and acidification in cultured human cancer cells, thereby promoting clonogenicity. In the absence of SOX2 expression, ACSS2 knockdown or supplementation with acetate provide a partial rescue. Together, these data indicate novel ribosome-based mechanistic contributions of pluripotency factors to stemness and cell fate determination.
2024-09-16 | PXD015157 | Pride
Project description:The objective of this study was to identify genes regulated by canonical Wnt signaling in mouse embryonic stem cells (ESCs).Canonical Wnt signaling supports the pluripotency of mouse ESCs but also promotes differentiation of early mammalian cell lineages. To explain these paradoxical observations, we explored the gene regulatory networks at play. Canonical Wnt signaling is intertwined with the pluripotency network comprising Nanog, Oct4, and Sox2 in mouse ESCs. In defined media supporting the derivation and propagation of mouse ESCs, Tcf3 and ?-catenin interact with Oct4; Tcf3 binds to Sox motif within Oct-Sox composite motifs that are also bound by Oct4-Sox2 complexes. Further, canonical Wnt signaling up-regulates the activity of the Pou5f1 distal enhancer via the Sox motif in mouse ESCs. When viewed in the context of published studies on Tcf3 and ?-catenin mutants, our findings suggest that Tcf3 counters pluripotency by competition with Sox2 at these sites, and Tcf3 inhibition is blocked by ?-catenin entry into this complex. Wnt pathway stimulation also triggers ?-catenin association at regulatory elements with classic Lef/Tcf motifs associated with differentiation programs. The failure to activate these targets in the presence of a MEK/ERK inhibitor essential for mouse ESC culture suggests that MEK/ERK signaling and canonical Wnt signaling combine to promote mouse ESC differentiation. Triplicates of mouse embryonic stem cells cultured with GSK3 inhibitor CHIR99021 or with Wnt pathway inhibitor XAV939.
2013-03-01 | E-GEOD-43420 | biostudies-arrayexpress
Project description:The functional consequences of cancer-associated missense mutations are unclear for majority of proteins, here we interrogated cancer mutation databases and identified recurrently mutated positions at structural contact interface of DNA-binding domains of SOX and POU family transcription factors. We used conversion of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs) as a functional read out. In this study we identified several gain-of-function mutations that enhance cellular pluripotency reprogramming by SOX2 and OCT4. Wild type SOX17 does not support pluripotency reprogramming while recurrent missense mutation SOX17-V118M converts SOX17 into a pluripotency inducer, viability of cancer cells and provides protein stability. Here, we conclude that mutational profile of SOX and OCT family factors in cancer association can give direction to design high-performance reprogramming factors.
2019-10-23 | GSE134930 | GEO