Genetic variation at transcription factor binding sites largely explains phenotypic heritability in maize

作者：Julia Engelhorn, Samantha J. Snodgrass, Amelie Kok, Arun S. Seetharam, Michael Schneider, Tatjana Kiwit, Ayush Singh, Michael Banf, Duong Doan, Merritt Khaipho-Burch, Daniel E. Runcie, Víctor A. Sánchez-Camargo, Rechien Bader, J. Vladimir Torres‐Rodríguez, Guangchao Sun, Maike Stam, Fabio Fiorani, Sebastian Beier, James C. Schnable, Hank W. Bass, Matthew B. Hufford, Benjamin Stich, Wolf B. Frommer, Jeffrey Ross‐Ibarra, Thomas Hartwig · 发表于：Nature Genetics · 年份：2025 · DOI：10.1038/s41588-025-02246-7 · 被引用次数：35 · 研究领域：Genetic Mapping and Diversity in Plants and Animals、Genetics and Plant Breeding、Plant Disease Resistance and Genetics

Comprehensive maps of functional variation at transcription factor (TF) binding sites (cis-elements) are crucial for elucidating how genotype shapes phenotype. Here, we report the construction of a pan-cistrome of the maize leaf under well-watered and drought conditions. We quantified haplotype-specific TF footprints across a pan-genome of 25 maize hybrids and mapped over 200,000 variants, genetic, epigenetic, or both (termed binding quantitative trait loci (bQTL)), linked to cis-element occupancy. Three lines of evidence support the functional significance of bQTL: (1) coincidence with causative loci that regulate traits, including vgt1, ZmTRE1 and the MITE transposon near ZmNAC111 under drought; (2) bQTL allelic bias is shared between inbred parents and matches chromatin immunoprecipitation sequencing results; and (3) partitioning genetic variation across genomic regions demonstrates that bQTL capture the majority of heritable trait variation across ~72% of 143 phenotypes. Our study provides an auspicious approach to make functional cis-variation accessible at scale for genetic studies and targeted engineering of complex traits.