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ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

ABSTRACT: The role of POU4F3 in Merkel cell maturation, but not induction, is similar to its role in hair cells. This prompted us to investigate whether POU4F3 also regulates the accessibility of ATOH1 targets in a feed-forward manner during the maturation of Merkel cells. Our results suggest that, just as in hair cells, the pioneer factor activity of POU4F3 is also required for ATOH1 to correctly coordinate mechanosensory differentiation in Merkel cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE150388 | 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

Project description:Hearing and balance are mediated in vertebrates by inner ear mechanosensory hair cells. Hair cell development, maturation and survival require POU4F3, a class IV POU domain transcription factor that is expressed in hair cells shortly after they start to differentiate. Here, we show that POU4F3 has pioneer factor activity, and is necessary to promote chromatin accessibility at approximately half of the distal regulatory elements that appear as hair cells differentiate. Pou4f3 expression in the inner ear is initiated by ATOH1, a bHLH transcription factor that is also necessary for hair cell differentiation and survival. We show that ATOH1 also binds a large number of POU4F3-dependent distal regulatory elements, suggesting a synergistic feed-forward model in which ATOH1 induces POU4F3, which then acts to promote ATOH1-dependent hair cell differentiation.

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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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Analyses of the Atoh1, Pou4f3 and Gfi1 genome binding profile during hair cell and neuronal differentiation

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Project description:We purified seven different cell populations and performed RNA sequencing to profile transcriptional similarities and differences between them. The seven cell types were 1) Atoh1-GFP positive cochlear hair cells from the organ of Corti of postnatal day one mice, 2) Atoh1-GFP negative cells from the organ of Corti of postnatal day one mice, 3) Atoh1-GFP positive induced hair cells generated by overexpression of Six1, Atoh1, Pou4f3, and Gfi1, 4) dsRed transduced control mouse embryonic fibroblasts, 5) Atoh1-GFP positive Merkel cells from postnatal day 1 mice, 6) Atoh1-GFP positive Cerebellar granule precursor cells from postnatal day 1 mice, and 7) Atoh1-GFP positive Gut secretory cells from postnatal day one mice.

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Generation of Inner Ear Hair Cells by Direct Lineage Conversion of Primary Somatic Cells [ATAC-seq]

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ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

Project description:ATACseq, CutnRun and RNAseq data from Merkel cell and Touch dome epithelial progenitor cells, from wild type and Pou4f3-mutant epidermis

| PRJNA631967 | ENA

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