Widespread Long-range Cis-Regulatory Elements in the Maize Genome

Genetic mapping studies on crops suggest that agronomic traits can be controlled by loci within the gene-distal intergenic space. Despite the biological importance and the potential agronomic utility of these intergenic loci, they remain virtually uncharacterized in all crop species to date. Here, we provide genetic, epigenomic, and functional molecular evidence supporting the widespread existence of gene-distal (hereafter, distal) loci which act as long-range transcriptional cis-regulatory elements (CREs) in the maize genome. Such loci are enriched for euchromatic chromatin features that suggest their regulatory functions. Chromatin loops link together putative CREs with genes and recapitulate eQTL-gene interactions. Additionally, putative CREs display elevated transcriptional enhancer activities, as measured by STARR-seq. These results provide functional support for the widespread existence of CREs which act over large genomic distances to modulate gene expression. Overall design: One MethylC-seq, six RNA-seq, 30 ChIP-seq, 37 DAP-seq, six ATAC-seq, one Hi-C, two HiChIP, and three STARR-seq samples of maize