Maternal pluripotency factors initiate extensive chromatin remodelling to predefine first response to inductive signals

Gentsch, George E.; Spruce, Thomas; Owens, Nick D.L.; Smith, James

doi:http://dx.doi.org/10.1038/s41467-019-12263-w

Maternal pluripotency factors initiate extensive chromatin remodelling to predefine first response to inductive signals

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Gentsch GE, Spruce T, Owens NDL, Smith JC. Maternal pluripotency factors initiate extensive chromatin remodelling to predefine first response to inductive signals. Nat Commun. 2019; 10(1):4269. DOI: 10.1038/s41467-019-12263-w

Abstract

Embryonic development yields many different cell types in response to just a few families of inductive signals. The property of signal-receiving cells that determines how they respond to inductive signals is known as competence, and it differs in different cell types. Here, we explore the ways in which maternal factors modify chromatin to specify initial competence in the frog Xenopus tropicalis. We identify early-engaged regulatory DNA sequences, and infer from them critical activators of the zygotic genome. Of these, we show that the pioneering activity of the maternal pluripotency factors Pou5f3 and Sox3 determines competence for germ layer formation by extensively remodelling compacted chromatin before the onset of inductive signalling. This remodelling includes the opening and marking of thousands of regulatory elements, extensive chromatin looping, and the co-recruitment of signal-mediating transcription factors. Our work identifies significant developmental principles that inform our understanding of how pluripotent stem cells interpret inductive signals.