OCT4-SOX2 dimers reshape the epigenome to promote neural crest multipotency [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA687495 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13293413.fastq.gz | Fastqsanger.gz | |||
| SRR13293414.fastq.gz | Fastqsanger.gz | |||
| SRR13293415.fastq.gz | Fastqsanger.gz | |||
| SRR13293416.fastq.gz | Fastqsanger.gz | |||
| SRR13293417.fastq.gz | Fastqsanger.gz |
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Project description:OCT4-SOX2 dimers reshape the epigenome to promote neural crest multipotency
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Project description:The transcription factors OCT4 and SOX2 play an essential role in the establishment and maintenance of pluripotent embryonic stem cells (ESCs). Yet, their function in specialized stem cell populations is still poorly understood. Here, we show that the OCT4 and SOX2 work as dimers to regulate the epigenomic landscape of neural crest cells. By isolating primary neural crest cells at a range of developmental stages, we characterized the transcriptomic and epigenomic changes that take place during specification, migration, and early differentiation. Analysis of these datasets revealed that the OCT4/SOX2 dimer promotes an epigenomic signature inherent to the multipotent neural crest. We found that the emergence of this epigenomic state requires the translocation of OCT4/SOX2 to tissue-specific cis-regulatory regions. By examining genome organization during the induction of hESCs into neural crest cells, we observed that the patterns of genomic occupancy of the dimer are modified during cell fate commitment. Dimer translocation is guided by neural crest-specific pioneer transcription factors, which physically interact with the OCT4/SOX to modify their genomic targets. Our results demonstrate how the ESC pluripotency program is repurposed in specialized stem cells to control chromatin organization and define the developmental potential of embryonic progenitors.
2022-09-06 | GSE163768 | GEO
Project description:The transcription factors OCT4 and SOX2 play an essential role in the establishment and maintenance of pluripotent embryonic stem cells (ESCs). Yet, their function in specialized stem cell populations is still poorly understood. Here, we show that the OCT4 and SOX2 work as dimers to regulate the epigenomic landscape of neural crest cells. By isolating primary neural crest cells at a range of developmental stages, we characterized the transcriptomic and epigenomic changes that take place during specification, migration, and early differentiation. Analysis of these datasets revealed that the OCT4/SOX2 dimer promotes an epigenomic signature inherent to the multipotent neural crest. We found that the emergence of this epigenomic state requires the translocation of OCT4/SOX2 to tissue-specific cis-regulatory regions. By examining genome organization during the induction of hESCs into neural crest cells, we observed that the patterns of genomic occupancy of the dimer are modified during cell fate commitment. Dimer translocation is guided by neural crest-specific pioneer transcription factors, which physically interact with the OCT4/SOX to modify their genomic targets. Our results demonstrate how the ESC pluripotency program is repurposed in specialized stem cells to control chromatin organization and define the developmental potential of embryonic progenitors.
2022-09-06 | GSE200196 | GEO
Project description:The transcription factors OCT4 and SOX2 play an essential role in the establishment and maintenance of pluripotent embryonic stem cells (ESCs). Yet, their function in specialized stem cell populations is still poorly understood. Here, we show that the OCT4 and SOX2 work as dimers to regulate the epigenomic landscape of neural crest cells. By isolating primary neural crest cells at a range of developmental stages, we characterized the transcriptomic and epigenomic changes that take place during specification, migration, and early differentiation. Analysis of these datasets revealed that the OCT4/SOX2 dimer promotes an epigenomic signature inherent to the multipotent neural crest. We found that the emergence of this epigenomic state requires the translocation of OCT4/SOX2 to tissue-specific cis-regulatory regions. By examining genome organization during the induction of hESCs into neural crest cells, we observed that the patterns of genomic occupancy of the dimer are modified during cell fate commitment. Dimer translocation is guided by neural crest-specific pioneer transcription factors, which physically interact with the OCT4/SOX to modify their genomic targets. Our results demonstrate how the ESC pluripotency program is repurposed in specialized stem cells to control chromatin organization and define the developmental potential of embryonic progenitors.
2022-09-06 | GSE163960 | GEO
Project description:The transcription factors OCT4 and SOX2 play an essential role in the establishment and maintenance of pluripotent embryonic stem cells (ESCs). Yet, their function in specialized stem cell populations is still poorly understood. Here, we show that the OCT4 and SOX2 work as dimers to regulate the epigenomic landscape of neural crest cells. By isolating primary neural crest cells at a range of developmental stages, we characterized the transcriptomic and epigenomic changes that take place during specification, migration, and early differentiation. Analysis of these datasets revealed that the OCT4/SOX2 dimer promotes an epigenomic signature inherent to the multipotent neural crest. We found that the emergence of this epigenomic state requires the translocation of OCT4/SOX2 to tissue-specific cis-regulatory regions. By examining genome organization during the induction of hESCs into neural crest cells, we observed that the patterns of genomic occupancy of the dimer are modified during cell fate commitment. Dimer translocation is guided by neural crest-specific pioneer transcription factors, which physically interact with the OCT4/SOX to modify their genomic targets. Our results demonstrate how the ESC pluripotency program is repurposed in specialized stem cells to control chromatin organization and define the developmental potential of embryonic progenitors.
2022-09-06 | GSE163771 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-09-02 | GSE163961 | GEO
Project description:Oct4 is a master regulator of pluripotency. Potential Oct4 interactors have been cataloged extensively but the manner and significance of these interactions are incompletely defined. Like other POU domain proteins, Oct4 is capable of binding to DNA in multiple configurations, however the relationship between these configurations and cofactor recruitment (and hence transcription output) are unknown. Here, we show that Oct4 interacts with common and unique proteins when bound to DNA in different configurations. One of these proteins is Jade1, a component of the HBO histone acetyltransferase complex. Jade1 preferentially associates with Oct4 when bound to More palindromic Octamer-Related Element (MORE) DNA sequences that bind Oct4 dimers and are associated with strong gene expression. We show that the Oct4 N-terminus is critical for this interaction. ChIP-seq using HBO1, the enzymatic component of the complex, identifies a preference for binding adjacent to Oct4 at MORE sites. Using purified recombinant proteins and nucleosome complexes, we show that the HBO1 complex acetylates histone H3K9 within nucleosomes more efficiently when Oct4 is co-bound to a MORE site. Histone acetylation is further increased when Oct4 is mutated to favor dimeric MORE binding. Cryo-electron microscopy reveals that Oct4 bound to a MORE near the nucleosome entry/exit site partially unwinds DNA from nucleosome core particles, and identifies additional mass associated with the HBO1 complex. These results identify a novel mechanism of transcriptional regulation by Oct4.
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