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| Status |
Public on Jul 30, 2021 |
| Title |
Rapid redistribution and extensive co-binding of NANOG and GATA6 at shared regulatory elements underlie specification of divergent cell fates [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Establishment of divergent cell types from a common progenitor requires transcription factors (TFs) to promote lineage-restricted transcriptional programs while suppressing alternative fates. In the mouse blastocyst, cells of the inner cell mass (ICM) coexpress NANOG and GATA6, two TFs that drive the bifurcation of these progenitors into either the epiblast (Epi) or the primitive endoderm (PrE), respectively. Here, using in vitro differentiation, we describe the molecular mechanisms of how GATA6 quickly induces the PrE fate while repressing the Epi lineage. GATA6 functions as a pioneer TF by inducing nucleosome repositioning at regulatory elements controlling PrE genes, making them accessible for deposition of active histone marks and leading to rewiring of chromatin interactions and ultimately transcriptional activation. GATA6 also binds most regulatory elements of Epi genes followed by eviction of the Epi-specific TFs NANOG and SOX2, loss of active histone marks, and reduction in chromatin accessibility that culminates in transcriptional repression. Unexpectedly, evicted NANOG and SOX2 transiently bind PrE regulatory elements occupied by GATA6. Our study shows that GATA6 binds and modulate the same regulatory elements as Epi TFs, a phenomenon we also validated in blastocysts. We propose that the ability of PrE and Epi-specific TFs to extensively bind and regulate the same gene networks contributes to ICM plasticity and allows rapid cell lineage specification by coordinating both activation and repression of divergent transcriptional programs.
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| Overall design |
Mapping changes in Nanog binding during in vitro differentiation of mouse embryonic stem cells into primitive endoderm.
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| Contributor(s) |
Rocha PP, Thompson JJ |
| Citation(s) |
35871075 |
|
https://www.biorxiv.org/content/10.1101/2021.07.28.454132v3
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| |
| Submission date |
Jul 29, 2021 |
| Last update date |
Aug 03, 2022 |
| Contact name |
Pedro P Rocha |
| E-mail(s) |
[email protected]
|
| Phone |
3014022426
|
| Organization name |
National Institutes of Health
|
| Department |
NICHD
|
| Lab |
Unit on Genome Structure and Regulation
|
| Street address |
6 Center Drive Building 6B 2B220
|
| City |
Bethesda |
| State/province |
Maryland |
| ZIP/Postal code |
20892-2785 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE181104 |
Rapid redistribution and extensive co-binding of NANOG and GATA6 at shared regulatory elements underlie specification of divergent cell fates |
|
| Relations |
| BioProject |
PRJNA750708 |
| SRA |
SRP330430 |
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