Genetic mapping studies on crops suggest that agronomic traits can be controlled by gene–distal intergenic loci. Despite the biological importance and the potential agronomic utility of these loci, they remain virtually uncharacterized in all crop species to date. Here, we provide genetic, epigenomic and functional molecular evidence to support the widespread existence of gene–distal (hereafter, distal) loci that act as long-range transcriptional cis-regulatory elements (CREs) in the maize genome. Such loci are enriched for euchromatic features that suggest their regulatory functions. Chromatin loops link together putative CREs with genes and recapitulate genetic interactions. Putative CREs also display elevated transcriptional enhancer activities, as measured by self-transcribing active regulatory region sequencing. These results provide functional support for the widespread existence of CREs that act over large genomic distances to control gene expression.
Bibliographical noteFunding Information:
This work was funded by the National Science Foundation (NSF) grant no. IOS-1546867 to R.J.S. and X.Z.; grant no. NSF IOS-1238142 to X.Z and M.J.S.; and grant no. NSF IOS-1456950 and NSF IOS-1546873 to A.G. F.J. and R.J.S. acknowledge support from the Technical University of Munich–Institute for Advanced Study funded by the German Excellent Initiative and the European Seventh Framework Programme under grant agreement no. 291763. F.J. is also supported by the SFB/Sonderforschungsbereich924 of the Deutsche Forschungsgemeinschaft. R.J.S. is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. M.C.-T. acknowledges support from the Impuls-und Vernetzungsfonds of the Helmholtz-Gemeinschaft (grant no. VH-NG-1219). J.Z. and his team is supported by the Programme for Guangdong Introducing Innovative and Entrepreneurial Teams (grant no. 2016ZT06S172). This work was supported in part by the National Institutes of Health Pathway to Independence Award no. K99/ R00 GM127671 (M.J.R.) and the US Public Health Service Award (R01) no. GM035463 (V.G.C.) from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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