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C-JUN is a pioneer factor safeguarding the primed state of pluripotency (RNA-Seq)

ABSTRACT: Mouse ESCs and EpiSCs represent naive and primed states of plurioptency corresponding to two consecutive stages of embryo development. Here we map their chromatin accessibility landscapes and show that naive specific open chromatin are enriched with motifs for Oct/Sox/Klf/TCF and primed one with AP1 motifs. The AP1 founding member c-Jun is expressed in EpiSCs and occupies both open and closed chromatin. Yet, c-Jun deficiency has no impact on the self renewal nor the transcription program of EpiSCs. However, in a Klf4-driven reprogramming system, we show that c-Jun-/- EpiSCs undergo primed to naive transition more efficiently than wild type cells and Klf4 evicts c-JUN from wild type chromatin. These results suggest that c-Jun is a pioneer factor not to regulate transcription but to prevent backward reprogramming during naive-primed transition, thus providing a molecular basis for the forward principle in development.

ORGANISM(S): Mus musculus

PROVIDER: GSE127925 | GEO | 2020/12/31

REPOSITORIES: GEO

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c-JUN is a pioneer factor safeguarding the primed state of pluripotency (ChIP-Seq)

Project description:Mouse ESCs and EpiSCs represent naive and primed states of plurioptency corresponding to two consecutive stages of embryo development. Here we map their chromatin accessibility landscapes and show that naive specific open chromatin are enriched with motifs for Oct/Sox/Klf/TCF and primed one with AP1 motifs. The AP1 founding member c-Jun is expressed in EpiSCs and occupies both open and closed chromatin. Yet, c-Jun deficiency has no impact on the self renewal nor the transcription program of EpiSCs. However, in a Klf4-driven reprogramming system, we show that c- Jun-/- EpiSCs undergo primed to naive transition more efficiently than wild type cells and Klf4 evicts c-JUN from wild type chromatin. These results suggest that c-Jun is a pioneer factor not to regulate transcription but to prevent backward reprogramming during naive-primed transition, thus providing a molecular basis for the forward principle in development.

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