Genetic variation at transcription factor binding sites largely explains phenotypic heritability in maize
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.
Authors
- Víctor A. Sánchez-Camargo (ORCID: https://orcid.org/0000-0002-7184-0301)
- Matthew B. Hufford (ORCID: https://orcid.org/0000-0003-3945-1143)
- Arun S. Seetharam (ORCID: https://orcid.org/0000-0002-6789-9298)
- Sebastian Beier (ORCID: https://orcid.org/0000-0002-2177-8781)
- Fabio Fiorani (ORCID: https://orcid.org/0000-0001-8775-1541)
- Michael Banf (ORCID: https://orcid.org/0000-0002-4312-6004)
- Hank W. Bass (ORCID: https://orcid.org/0000-0003-0522-0881)
- Julia Engelhorn (ORCID: https://orcid.org/0000-0002-6680-3012)
- Samantha J. Snodgrass (ORCID: https://orcid.org/0000-0001-9209-6051)
- Maike Stam (ORCID: https://orcid.org/0000-0003-0363-4677)
- Duong Doan
- James C. Schnable (ORCID: https://orcid.org/0000-0001-6739-5527)
- Merritt Khaipho-Burch (ORCID: https://orcid.org/0000-0002-1503-6853)
- Thomas Hartwig (ORCID: https://orcid.org/0000-0002-2707-2771)
- J. Vladimir Torres‐Rodríguez (ORCID: https://orcid.org/0000-0001-6056-3452)
- Rechien Bader (ORCID: https://orcid.org/0009-0001-4738-190X)
- Wolf Bernd Frommer (ORCID: https://orcid.org/0000-0001-6465-0115)
- Daniel E. Runcie (ORCID: https://orcid.org/0000-0002-3008-9312)
- Michael Schneider (ORCID: https://orcid.org/0000-0002-6491-8852)
- Jeffrey Ross‐Ibarra (ORCID: https://orcid.org/0000-0003-1656-4954)
- Benjamin Stich (ORCID: https://orcid.org/0000-0001-6791-8068)
- Guangchao Sun (ORCID: https://orcid.org/0000-0003-3942-6175)
- Tatjana Kiwit
- Ayush Singh
- Amelie Kok (ORCID: https://orcid.org/0009-0009-5930-5232)
Institutions
- Florida State University (US)
- University of Nebraska–Lincoln (US)
- Centre de Coopération Internationale en Recherche Agronomique pour le Développement (FR)
- Julius Kühn-Institut (DE)
- Forschungszentrum Jülich (DE)
- Iowa State University (US)
- Université de Montpellier (FR)
- Cornell University (US)
- Sichuan Agricultural University (CN)
- Diversité, adaptation et développement des plantes (FR)
- Cluster of Excellence on Plant Sciences (DE)
- Max Planck Institute for Plant Breeding Research (DE)
- Institut de Recherche pour le Développement (FR)
- Heinrich Heine University Düsseldorf (DE)
- Nagoya University (JP)
- University of California, Davis (US)
- University of Amsterdam (NL)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1038/s41588-025-02246-7
- Citations
- 8
- Primary Topic
- Genetic Mapping and Diversity in Plants and Animals
- Type
- article
- Field-Weighted Citation Impact
- 14.54
Funders
- National Science Foundation
- U.S. Department of Energy
- U.S. Department of Agriculture
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Horizon 2020 Framework Programme