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 two-hundred thousand genetic variants (termed binding-QTL) linked to cis-element occupancy. Three lines of evidence support the functional significance of binding-QTL: i) they coincide with numerous known causative loci that regulate traits, including VGT1, Trehalase1, and the MITE transposon near ZmNAC111 under drought; ii) their footprint bias is mirrored between inbred parents and by ChIP-seq; iii) partitioning genetic variation across genomic regions demonstrates that binding-QTL capture the majority of heritable trait variation across ∼70% of 143 phenotypes. Our study provides a promising approach to make previously hidden cis-variation more accessible for genetic studies and multi-target engineering of complex traits.

• Publication year

  2024

• Venue

  bioRxiv

• Publication date

  2024-04-20

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1038/s41588-025-02246-7PMID 40789919PMCID 12425805
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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