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Series GSE87819 Query DataSets for GSE87819
Status Public on Mar 13, 2017
Title The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells [ATAC-Seq]
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary 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.
Overall design ZHBTC4 and Brg1fl/fl mouse embryonic stem cells were used to ablate OCT4 and BRG1 expression respectively, followed by ATAC-seq, ChIP-seq or RNA-seq to examine their contribution towards chromatin accessibility, transcription factor occupancy, and gene expression.
Contributor(s) King HW, Klose RJ
Citation(s) 28287392
Submission date Oct 11, 2016
Last update date May 15, 2019
Contact name Hamish W King
Organization name Queen Mary University of London
Department Blizard Institute
Street address 4 Newark St
City London
ZIP/Postal code E1 2AT
Country United Kingdom
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (13)
GSM2341271 ZHBTC4_ATAC_UNT_rep1 (ATAC-Seq)
GSM2341272 ZHBTC4_ATAC_UNT_rep2 (ATAC-Seq)
GSM2341273 ZHBTC4_ATAC_UNT_rep3 (ATAC-Seq)
This SubSeries is part of SuperSeries:
GSE87822 The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells
BioProject PRJNA347886
SRA SRP091442

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Supplementary file Size Download File type/resource
GSE87819_RAW.tar 208.4 Mb (http)(custom) TAR (of BW) 435.6 Mb (ftp)(http) BW 423.6 Mb (ftp)(http) BW 470.3 Mb (ftp)(http) BW 449.7 Mb (ftp)(http) BW
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Processed data are available on Series record

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