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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE122937 | GEO | 2020/06/16

REPOSITORIES: GEO

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ATAC-Seq]

Project description:Mouse naive and primed pluripotent stem cells, ESC and EpiSC, represent two distinct stages of pluripotency. Here we report that BMP4 drives primed to naive transition or PNT by reprogramming chromatin accessibility. ATAC-seq reveals that a short pulse of BMP4 triggers EpiSCs to close 26409 and open 6428 loci to reach an intermediate state that continue to open 18744 and close 7042 loci under 2iL until reaching a naive state, following with a dramatic reactivation of the silenced X chromosome. Among loci opened by BMP4 are those encoding Id1, Tfap2c/2a and Zbtb7b that synergistically drive PNT without BMP4. Tfap2c-/- ESCs or EpiSCs self-renew normally, while the former capable of differentiating to the latter but the latter fails to undergo PNT, a defect rescuable by exogenous Tfap2c. Our results link BMP4 to PNT through a binary logic of chromatin closing and opening, revealing the intrinsic power of extracellular factors to reorganize nuclear architecture in development.

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [RNA-Seq]

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

Project description:BMP4 regulates a plethora of developmental processes including dorsal-ventral axis and neural patterning. Here we report that BMP4 reconfigures nuclear archi-tecture during primed to naive transition (PNT). We first established a robust BMP4 driven PNT and shown by ATAC- and RNA-seq that it orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a/b as new targets that contribute to drive PNT. Mechanically, BMP first activates Zbtb7a/b in both chromatin and gene expression level, which in turn facilitate the opening of naïve pluripotent chromatin loci and allow the activation of naïve pluripotent genes. Surprisingly, Zbtb7a not only binds to chromatin loci near the genes to be activated, but also strategically occupies those to be silenced, thus resolving the conflicting role of BMP4 in both activating and suppressing gene ex-pression during PNT at the chromatin level. Our results reveal a previously un-known function of BMP4 in regulating nuclear architecture and link its targets Zbtb7a/b to chromatin remodeling and pluripotent fate control.

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

Project description:BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

| PRJNA506966 | ENA

BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

Project description:BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

| PRJNA611573 | ENA

BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [RNA-Seq]

Project description:BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [RNA-Seq]

| PRJNA506967 | ENA

BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ATAC-Seq]

Project description:BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ATAC-Seq]