OTX2 controls chromatin accessibility to direct somatic versus germline differentiation [CUT&Run]
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ABSTRACT:
PROVIDER: PRJNA1222361 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32310058_1.fastq.gz | Fastqsanger.gz | |||
| SRR32310058_2.fastq.gz | Fastqsanger.gz | |||
| SRR32310059_1.fastq.gz | Fastqsanger.gz | |||
| SRR32310059_2.fastq.gz | Fastqsanger.gz | |||
| SRR32310060_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:The choice between somatic and germline fates is essential for species survival. This choice occurs in embryonic epiblast cells, as these cells are competent for both somatic and germline differentiation. Transcription factors (TFs) play a central role in this process by binding to specific chromatin loci to modulate gene expression and determine cell identity. The TF OTX2 regulates the choice between somatic and germline fates, as Otx2-null epiblast-like cells (EpiLCs) form primordial germ cell-like cells (PGCLCs) with enhanced efficiency. However, the mechanisms by which OTX2 achieves this function are not fully characterized. Here we show that OTX2 controls chromatin accessibility to enable somatic differentiation. By performing CUT&RUN for OTX2 and ATAC-seq in wild-type and Otx2-null embryonic stem cells and EpiLCs, we identified regions where OTX2 binding opens chromatin. Enforced OTX2 expression maintains accessibility at these regions and induces opening of 4,000 additional somatic-associated regions in the presence of PGC-inducing cytokines. Once cells have acquired germline identity, the 4,000 additional somatic associated regions do not respond to OTX2 and remain closed. Our results indicate that OTX2 works in cells with dual competence for both somatic and germline differentiation to increase accessibility of somatic regulatory regions and induce the somatic fate at the expense of the germline.
2025-02-17 | GSE289297 | GEO
Project description:The choice between somatic and germline fates is essential for species survival. This choice occurs in embryonic epiblast cells, as these cells are competent for both somatic and germline differentiation. Transcription factors (TFs) play a central role in this process by binding to specific chromatin loci to modulate gene expression and determine cell identity. The TF OTX2 regulates the choice between somatic and germline fates, as Otx2-null epiblast-like cells (EpiLCs) form primordial germ cell-like cells (PGCLCs) with enhanced efficiency. However, the mechanisms by which OTX2 achieves this function are not fully characterized. Here we show that OTX2 controls chromatin accessibility to enable somatic differentiation. By performing CUT&RUN for OTX2 and ATAC-seq in wild-type and Otx2-null embryonic stem cells and EpiLCs, we identified regions where OTX2 binding opens chromatin. Enforced OTX2 expression maintains accessibility at these regions and induces opening of 4,000 additional somatic-associated regions in the presence of PGC-inducing cytokines. Once cells have acquired germline identity, the 4,000 additional somatic associated regions do not respond to OTX2 and remain closed. Our results indicate that OTX2 works in cells with dual competence for both somatic and germline differentiation to increase accessibility of somatic regulatory regions and induce the somatic fate at the expense of the germline.
2025-02-17 | GSE289298 | GEO
Project description:OTX2 controls chromatin accessibility to direct somatic versus germline differentiation [ATAC-Seq]
| PRJNA1222363 | ENA
Project description:We discovered a role for the transcription factor OTX2 in formation of mouse definitive endoderm (DE). We used CUT&RUN to map OTX2-bound genomic regions and identify OTX2-regulated genes during directed differentiation of EpiSCs to DE
2024-06-26 | GSE254590 | GEO
Project description:The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast. Induction requires BMP4 signalling to prospective PGCs and the intrinsic action of PGC transcription factors (TFs). However, the molecular mechanisms connecting BMP4 action to induction of PGC TFs that are responsible for segregation of PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Down-regulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro dramatically increases PGCLC differentiation efficiency and prolongs the period of PGC competence. In the absence of Otx2 activity, PGCLC differentiation becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC TF Blimp1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that Otx2 acts repressively upstream of PGC TFs and functions as a roadblock to prevent the untimely entry of pluripotent stem cells into the PGC lineage, thereby ensuring correct spatio-temporal segregation of the germline and soma.
2018-07-06 | GSE116640 | GEO
Project description:The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling *** This Series represents the gene expression component of the study. Three independent time course experiments of OTX2 silencing, and 1 control experiment in D425 medulloblastoma cells.
2012-07-03 | E-GEOD-22875 | biostudies-arrayexpress
Project description:The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients. Keywords: OTX2, medulloblastoma, mRNA profiling
2012-07-04 | GSE22875 | GEO
Project description:Segregation of the mammalian germline and soma is policed by Otx2
| PRJNA479763 | ENA
Project description:Otx2 has been shown to be non cell autonomously required for photoreceptor cell survival in the adult mouse RPE. This study aims to identify Otx2 DNA binding profile in both RPE and neural retina to i) identify direct targets of Otx2 in the RPE ii) compare Otx2 binding profile in neural retina and RPE to unveil hidden functions in the neural retina. WT and GFP antibodies were used to perform two independent ChIP-seq experiments using Illumina GAIIx.
2014-01-15 | E-GEOD-54084 | biostudies-arrayexpress
Project description:The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. We generated Otx2 conditional knockout (cKO) mice to investigate its roles in telencephalon development after E9.0. We conducted transcriptional profiling and in situ hybridization to identify genes de-regulated in Otx2 cKO ventral forebrain. In parallel, we used ChIP-seq to identify enhancer elements, OTX2 binding motif, and which de-regulated genes are likely direct targets of Otx2 transcriptional regulation. We found that Otx2 was essential in septum specification; regulation of Fgf signaling in the rostral telencephalon; and medial ganglionic eminence (MGE) patterning, neurogenesis, and oligodendrogenesis. Within the MGE, Otx2 was required for ventral but not dorsal identity; this is the first demonstration of a transcription factor that contributes to regional patterning within the MGE. Microdissected subpallium (septum, MGE, and LGE ) from wildtype E12.5 CD-1 embryos was used in three independentanti-OTX2 ChIP-seq experiments.
2015-06-10 | E-GEOD-69724 | biostudies-arrayexpress