Abstract
The ability of cells to respond to intercellular signals, and the repertoire of possible responses to those signals, is defined by their ‘competence’, a long-standing developmental concept1, that is key to tissue formation and tissue regeneration. Apart from a few cell type-specific transcription factors2, little is known about the role of the chromatin landscape in defining competence. Here, we investigate the emergence of competence in Xenopus tropicalis, which, like most multicellular organisms, begins development with a transcriptionally silent genome. We first identified the earliest functional regulatory DNA sequences, and inferred from them the critical sequence-specific activators of the zygotic genome. Of these, we showed that the maternal pluripotency factors Pou5f3 and Sox3 specifically open thousands of compacted chromatin sites by recognising their canonical DNA binding sequences. This pioneering activity initiates local chromatin remodelling to facilitate poised or active transcription, including the post-translational marking of displaced nucleosomes and chromatin looping with promoters. These remodelled chromatin sites are then capable of responding to intercellular signalling by recruiting the signal mediators that convert signals into tissue-specific expression of developmentally critical genes. As well as shedding light on genome activation and competence, our findings suggest that transcriptional responses to signals can be re-awakened by overexpressing the appropriate pioneer factors—a much sought-after objective in cell replacement therapies.
