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Using Mouse Embryonic Fibroblast to test the pioneer factor activity of POU4F3

ABSTRACT: Previous unbiased screening for the nucleosome binding affinity of transcription factors predicts that POU domain transcription factors have strong nucleosome binding potential. Here using reprogramming strategy we found that POU4F3 has pioneer factor activity at ATOH1 target elements that require POU4F3 for their accessibility.

ORGANISM(S): Mus musculus

PROVIDER: GSE150279 | GEO | 2021/07/09

REPOSITORIES: GEO

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ATACseq, CutnRun and RNAseq data from sensory progenitors and hair cells, from wild type and Pou4f3-mutant cochlea

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POU4F3 Pioneer Activity Enables ATOH1 to Drive Diverse Mechanoreceptor Differentiation Through a Feed-Forward Epigenetic Mechanism

Project description:During embryonic development, hierarchical cascades of transcription factors interact with lineage specific chromatin structures to control the sequential steps in the differentiation of specialized cell types. While examples of transcription factor cascades have been well documented, the mechanisms underlying developmental changes in accessibility of cell type-specific enhancers remain poorly understood. Here we show that the transcriptional ‘master regulator’, ATOH1 – which is necessary for the differentiation of two distinct mechanoreceptor cell types, hair cells in the inner ear, and Merkel cells of the epidermis – is unable to access much of its target enhancer network in the progenitor populations of either cell type when it first appears, imposing a block to further differentiation. This block is overcome by a feed-forward mechanism in which ATOH1 first stimulates expression of POU4F3, which subsequently acts as a pioneer factor to provide access to closed ATOH1 enhancers, allowing hair cell and Merkel cell differentiation to proceed. Our analysis also indicates the presence of both shared and divergent ATOH1/POU4F3-dependent, enhancer networks in hair cells and Merkel cells. These cells share a deep developmental lineage relationship, deriving from their common epidermal origin, and suggesting that this feed-forward mechanism preceded the evolutionary divergence of these very different mechanoreceptive cell types.

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Nucleosome binding by the pioneer transcription factor OCT4

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Project description: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.

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