Authors
Srushtideep Angidi, Khizar Razzaq
Published in
Molecular biology reports. Volume 53. Issue 1. Jul 10, 2026. Epub Jul 10, 2026.
Abstract
WRKY transcription factors are among the largest plant-specific transcription factor families and play central roles in coordinating gene expression during biotic and abiotic stress. Despite decades of research, a fundamental paradox remains: WRKY proteins bind short, widely distributed W-box cis-elements yet generate highly selective, context-dependent transcriptional outputs in vivo. In this review, we argue that WRKY specificity is not determined by DNA binding alone but emerges from the integration of five regulatory layers: cis-regulatory motif grammar, chromatin accessibility and epigenetic state, protein-protein interactions, post-translational modifications and proteostasis, and signaling context, which we collectively define as the WRKY regulatory code. We discuss how chromatin state controls which genomic W-box sites are physically accessible, while post-translational modifications and cofactor interactions determine which accessible sites are productively engaged and whether the transcriptional output is activation or repression. Representative mechanistic examples illustrate how different combinations of these regulatory layers generate precise, condition-dependent transcriptional programs. We further discuss how multi-omics integration and machine learning-based predictive modeling can decode and empirically test this regulatory code across stresses, tissues, and developmental contexts. The regulatory code perspective resolves key inconsistencies in WRKY biology and provides a practical conceptual framework for more targeted manipulation of stress-responsive transcriptional networks in crops.
PMID:
42430021
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.
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