ArticleProceedings of the National Academy of Sciences of the United States of America2021
POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
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- Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues.Frontiers in cell and developmental biology · 2026Review
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- Conditional Overexpression of Serpine2 Promotes Hair Cell Regeneration from Lgr5+ Progenitors in the Neonatal Mouse Cochlea.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs).BMC molecular and cell biology · 2025Article
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- POU4F3 Is Necessary for Normal Merkel Cell Formation, whereas POU4F1 Is Dispensable.The Journal of investigative dermatology · 2025Article
- Long-rangeProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Runx3, Brn3a and Isl1 interplay orchestrates the transcriptional program in the early stages of proprioceptive neuron development.PLoS genetics · 2024Article
- Highly compromised auditory spatial perception in aided congenitally hearing-impaired and rapid improvement with tactile technology.iScience · 2024Article
- A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.Developmental cell · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.