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Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering

Libin Zhang1* and Maoteng Li1, 2*   

  1. 1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 China
    2. Biological Seed Industry Research Institute, Xianghu Laboratory, Hangzhou, 311231 China
    *Correspondences: Libin Zhang (libinzhang@hust.edu.cn, Dr. Zhang is fully responsible for the distribution of all materials associated with this article); Maoteng Li (limaoteng426@hust.edu.cn)
  • Received:2026-07-06 Accepted:2026-08-24 Online:2026-09-08
  • Supported by:
    This study was supported by the National Natural Science Foundation of China (32572364).

Abstract: Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

Key words: artificial intelligence, cis-regulatory elements, multidimensional context, programmable crop engineering, transcriptional regulation

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