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 (epi)genetic variants (termed binding-QTL) linked to cis-element occupancy. Three lines of evidence support the functional significance of binding-QTL: i) coincidence with causative loci that regulate traits, including VGT1, ZmTRE1, and the MITE transposon near ZmNAC111 under drought; ii) bQTL allelic bias is shared between inbred parents and matches ChIP-seq results, iii) partitioning genetic variation across genomic regions demonstrates that binding-QTL 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. MOA-seq was performed in leaf blades of 25 maize F1 hybrids under well-watered and drought conditions. Please note that each processed data file was generated from multiple replicates and thus linked as Series supplementary file. The sample_to_processed_data.readme.txt list which samples each file belongs to. We further note that all F1 MOA/RNA data was mapped to diploid genomes created by concatenating the B73 V5 genome with the respective paternal genome (NAM v1 / 2 genomes18, Mo17 CAU v1, W22 v220, A188 v119, and A619) with the accession ID added as prefix to the chromosome name.