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The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells

ABSTRACT: The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells

PROVIDER: PRJNA347811 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4413780_1.fastq.gz	Fastqsanger.gz
	SRR4413780_2.fastq.gz	Fastqsanger.gz
	SRR4413790_1.fastq.gz	Fastqsanger.gz
	SRR4413790_2.fastq.gz	Fastqsanger.gz
	SRR4413800_1.fastq.gz	Fastqsanger.gz

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The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells [RNA-Seq]

Project description:Pioneer transcription factors are able to recognise and bind their motif sequences in inaccessible or closed chromatin, and their ability to achieve this is required to establish new regulatory elements and transcriptional networks during development and cellular reprogramming. An essential feature of this pioneering activity is the transition from inaccessible chromatin to a nucleosome-depleted and accessible chromatin state typical of normal regulatory elements, and this is believed to facilitate further transcription factor binding events. However, the mechanisms by which many pioneer transcription factors achieve this remarkable feat remain elusive. Here we reveal that the pluripotency-associated pioneer factor OCT4 binds inaccessible chromatin to shape the chromatin accessibility, transcription factor co-binding and regulatory potential of thousands of distal regulatory elements in mouse embryonic stem cells, demonstrating that its pioneering activity is a feature of normal pluripotency, and not just reprogramming. The accessible chromatin formed at OCT4 binding sites relies on the chromatin remodelling factor BRG1, which is recruited to these sites by OCT4. The occupancy of BRG1 is then required to support OCT4/SOX2 co-binding and normal expression of the pluripotency-associated transcriptome, and this reliance on BRG1 reflects OCT4 binding dynamics during cellular reprograming and early mouse development. Together these observations reveal a distinct requirement for the chromatin remodelling factor BRG1 in shaping the pioneering activity of OCT4 and regulating the pluripotency network in embryonic stem cells.

2017-03-13 | GSE87821 | GEO

The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells [ChIP-Seq]

2017-03-13 | GSE87820 | GEO

The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells [ATAC-Seq]

2017-03-13 | GSE87819 | GEO

The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells.

Project description:Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming. During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this. Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells. Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 to support additional transcription factor binding and expression of the pluripotency-associated transcriptome. Furthermore, the requirement for BRG1 in shaping OCT4 binding reflects how these target sites are used during cellular reprogramming and early mouse development. Together this reveals a distinct requirement for a chromatin remodeller in promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network.

| S-EPMC5400504 | biostudies-literature

Nucleosome binding by the pioneer transcription factor OCT4

Project description:The nucleosome is a fundamental unit of chromatin in eukaryotes, and generally prevents the binding of transcription factors to genomic DNA. Pioneer transcription factors overcome the nucleosome barrier, and bind their target DNA sequences in chromatin. OCT4 is a representative pioneer transcription factor that plays a role in stem cell pluripotency. In the present study, we biochemically analyzed the nucleosome binding by OCT4. Crosslinking mass spectrometry showed that OCT4 binds the nucleosome.

2020-05-13 | PXD019160 | JPOST Repository

The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells

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

2017-03-13 | GSE87822 | GEO

Genome-wide occupancy of chromatin remodeller SMARCAL1 and BRG1 in human cells

Project description:Genome-wide occupancy of chromatin remodeller SMARCAL1 and BRG1 in human cells

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BRG1 governs Glucocorticoid Receptor interactions with chromatin and pioneer factors across the genome

Project description:The Glucocorticoid Receptor (GR) alters transcriptional activity in response to hormones by interacting with chromatin at GR binding sites (GBSs) throughout the genome. Our work in human breast cancer cells identifies three classes of GBSs with distinct epigenetic characteristics and reveals that BRG1 interacts with GBSs prior to hormone exposure. The GBSs pre-occupied by BRG1 are more accessible and transcriptionally active than other GBSs. BRG1 is required for a proper and robust transcriptional hormone response and knockdown of BRG1 blocks recruitment of the pioneer factors FOXA1 and GATA3 to GBSs. Finally, GR interaction with FOXA1 and GATA3 binding sites was restricted to sites pre-bound by BRG1. These findings demonstrate that BRG1 establishes specialized chromatin environments that define multiple classes of GBS. This in turn predicts that GR and other transcriptional activators function via multiple distinct chromatin-based mechanisms to modulate the transcriptional response.

2018-05-22 | GSE112491 | GEO

Dissecting OCT4 defines the role of nucleosome binding in reprogramming

Project description:The aim of this study is to dissect the transcription factor OCT4 and reveal which parts of the protein are essential for interaction with nucleosomes and access to closed chromatin. We revealed that the DNA-binding domain mediates the interaction of OCT4 with nucleosomes. Remarkably, nucleosome-binding can be uncoupled from DNA-binding, diminishing the ability of OCT4 to access to closed chromatin, thus losing the pioneer function. We show that the pioneer function of OCT4 is not only essential during reprogramming differentiated cells to pluripotency but also during pluripotency maintenance of embryonic stem cells. Overall, this study shows how pioneer transcription factors interact with nucleosomes to engage the genome and control cellular identity, highlighting that nucleosomes are not always barriers to genome accessibility .

2021-06-24 | GSE167632 | GEO

Protein-protein interactions of BRG1 or BRG1-HSA in SW13 cells

Project description:The SWI/SNF complex remodels chromatin in an ATP-dependent manner through the ATPase subunits BRG1 and BRM. Chromatin remodeling alters nucleosome structure to change gene expression, however aberrant remodeling and gene expression can result in cancer. The function and localization on chromatin of the SWI/SNF complex depends on the protein makeup of the complex. Here we report the protein-protein interactions of wild-type BRG1 or mutant BRG1 in which the HSA domain has been deleted (BRG1-HSA). We demonstrate the interaction of BRG1 with most SWI/SNF complex members and a failure of a number of these members to interact with BRG1-HSA. These results demonstrate that the HSA domain of BRG1 is a critical interaction platform for the correct formation of SWI/SNF remodeling complexes.

2023-02-15 | PXD029647 | Pride

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