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- W2974245583 abstract "Abstract The first lineage specification of pluripotent mouse epiblast segregates neuroectoderm (NE) from mesoderm and endoderm (ME) by currently poorly understood mechanisms. Here we demonstrate that the induction of any ME-gene programs critically relies on the T-box (Tbx) transcription factors Eomes and Brachyury that concomitantly repress pluripotency and NE gene programs. Tbx-deficient cells retain pluripotency and differentiate to NE lineages despite the presence of ME-inducing signals TGFβ/Nodal and WNT. Pluripotency and NE gene networks are additionally repressed by Tbx-induced ME factors, demonstrating a remarkable redundancy in program regulation to safeguard mutually exclusive lineage specification. Chromatin analyses revealed that accessibility of ME-gene enhancers depends on Tbx-binding, while NE-gene enhancers are accessible and activation-primed already at pluripotency state. This asymmetry of chromatin landscape thus explains the default differentiation of pluripotent cells to NE in the absence of ME-induction mediated through the activating and repressive functions of early Tbx factors Eome s and Brachyury ." @default.
- W2974245583 created "2019-09-26" @default.
- W2974245583 creator A5017990911 @default.
- W2974245583 creator A5032632668 @default.
- W2974245583 creator A5033802517 @default.
- W2974245583 creator A5036005224 @default.
- W2974245583 creator A5036324176 @default.
- W2974245583 creator A5037203286 @default.
- W2974245583 creator A5052654483 @default.
- W2974245583 creator A5066595684 @default.
- W2974245583 creator A5067719557 @default.
- W2974245583 creator A5069176236 @default.
- W2974245583 creator A5089422027 @default.
- W2974245583 date "2019-09-23" @default.
- W2974245583 modified "2023-09-26" @default.
- W2974245583 title "Eomes and Brachyury control pluripotency exit and germ layer segregation by changes of chromatin state" @default.
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