Our observation that lncRNAs might be selectively regulated by a distinct set of TFs has substantial implications for systems biology: cells are potentially capable of harnessing a defined subset of regulatory switches to toggle the expression levels of lncRNAs without altering mRNA levels. Most of the disease-associated sequence variants in the human genome are non-coding [66], necessitating an integration of lncRNA TSS and exon locations with the increasingly abundant common-variant Genome Wide Association Studies (GWAS), as well as throughout whole-exome and whole-genome resequencing datasets designed to capture rare, large-effect disease-associated variants. Our results empower the GWAS community to re-annotate cryptic disease-associated variants at in silico predicted TFBSs that we have linked to global catalogs of lncRNA promoters and to lncRNA regulatory programs modulated by specific TFs. By virtue of their TFBS localization, such variants may emerge as direct functional candidates.
