ArticleCurrent issues in molecular biology2026
Functional Dissection of TP63 Dual-Promoter Regulatory Elements Reveals Context-Dependent Responsiveness to FOXA2, NKX2-1, SOX9, and TP63-Related Inputs.
Article in Current issues in molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The TP63 locus generates TAp63 and ΔNp63 isoforms through alternative promoter usage, but the cis-regulatory features that confer differential promoter responsiveness remain incompletely defined. Here, we functionally dissected distal TAp63-associated and proximal ΔNp63-associated TP63 promoter regions using reporter-based assays in A549 cells. Rabbit TP63 promoter fragments were selected from distal and proximal promoter-associated regions and analyzed by serial deletion and site-directed mutagenesis. Deletion mapping identified discrete promoter intervals that positively or negatively affected reporter activity, while motif perturbation revealed promoter-context-dependent contributions of predicted FOXA1/2, NKX2-1, SOX9, and TP63-related regulatory elements. Endogenous ChIP-qPCR at corresponding human TP63 promoter-associated regions provided local enrichment evidence for selected transcription-factor-associated signals, and FOXA2 or SOX9 depletion shifted endogenous TAp63 and ΔNp63 protein abundance. These findings identify candidate TP63 promoter intervals and transcription-factor-responsive motifs that differentially affect dual-promoter reporter output. The study provides a promoter-level framework for investigating how TP63 promoter responsiveness is influenced by promoter architecture, motif composition, and cellular regulatory background within a heterologous reporter context, while highlighting the need for future validation in more physiological human epithelial systems.
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