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Nucleosome-mediated competition of pioneer transcription factors

ABSTRACT: Pioneer transcription factors Nanog, Pou5f3 and Sox19b promote chromatin accessibility on the enhancers of the early zebrafish embryos. It is poorly understood how they act together; it is commonly assumed that they act additively or cooperatively to clear chromatin from the nucleosomes. We investigated this question by comparing chromatin accessibility (Omni ATAC-seq) in seven mutant genotypes: single, double and triple maternal-zygotic mutants by Pou5f3, Sox19b and Nanog, and the wild-type embryos. We found, that at most of the directly bound sites, either Pou or Nanog is required for chromatin accessibility; while at the minority of the sites two factors act additively. Further, on the sites, where Pou5f3 promotes chromatin accessibility, Nanog often suppresses it, and vice versa. To explain this phenomenon, we suggest a model of nucleosome-mediated competition between pioneer transcription factors: Pou5f3 and Nanog compete for the same binding motif on the DNA, but only one of the factors has a pioneer activity on this site. This entry contains only part fo the Omni-ATAC-seq experiments, the other part is in the previously released entry GSE188364.

ORGANISM(S): Danio rerio

PROVIDER: GSE215956 | GEO | 2023/08/02

REPOSITORIES: GEO

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Regulation of chromatin accessibility in early zebrafish embryos by Pou5f3 and Sox19b transcription factors.

Project description:Pou5f3 and Sox19b transcription factors promote chromatin accessibility and activate zygotic transcription in zebrafish embryos. It is poorly understood how two transcription factors act together on chromatin. To answer this question, we performed Omni-ATAC-seq on the zebrafish embryos, single and double mutants by Pou5f3 and Sox19b, as well as the wild-type, at two blastula developmental stages, oblong and dome. We report, that chromatin accessibility on 48% of all putative enhancers depends on Pou5f3 and Sox19b. Out of them, accessibility on 33% enhancers is reduced in the double mutant and of 15% is increased. Enhancers with reduced and increased chromatin accessibility differ in GC content and transcription factors binding motif frequency, and are linked to early and late developmental regulatory genes, respectively. Our results indicate that Pou5f3 and Sox19b not only activate early zygotic genes, but also prevent premature activation of late developmental enhancers.

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2023-10-24 | PXD043672 | Pride

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