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. 2021 Jul 15;118(29):e2105137118. doi: 10.1073/pnas.2105137118

Fig. 7.

Fig. 7.

Working model: ATOH1/POU4F3 feed-forward circuit controls the differentiation of hair cells and Merkel cells. (A) POU4F3 is a direct target of ATOH1. ATOH1 is up-regulated in the inner ear sensory progenitors and the TDEPs during their differentiation. ATOH1 binds to pre-established enhancers upstream of the Pou4f3 gene to stimulate the expression of POU4F3. (B) POU4F3 has pioneer factor activity. POU4F3 can recognize its cognate motifs in nucleosome-occupied DNA and is required for ATOH1 binding in closed chromatin. The binding of POU4F3 and ATOH1 does not result in the opening or the activation of the regulatory elements in the closed chromatin. (C) Context-dependent opening and activation of POU4F3-dependent ATOH1 targets. POU4F3, ATOH1, and other hair cell–specific transcription factors/cofactors can open and activate an array of hair cell–specific enhancers for mechanosensory differentiation in hair cells (e.g., stereocilia) tip link mechanotransduction apparatus formation. On the other hand, POU4F3, ATOH1, and other Merkel cell–specific transcription factors/cofactors can open and activate an array of Merkel cell–specific enhancers for mechanosensory differentiation in Merkel cells.