interactions that join lncRNAs and NHRs in ribonucleoprotein complexes – in turn, may regulate lncRNA transcription through promoter binding. Among the other TFs we considered, GATA3, ARID3A, and MEF2A have the singular distinction of being significantly supported by all three lines of evidence: TFBS motif enrichment at our 18,000 lncRNA promoters, DNase I hypersensitive site overrepresentation at their TFBS-containing lncRNA promoters, and ChIP-seq experimental evidence of enriched binding at these promoters genome-wide, across the ENCODE DNase I- and ChIP-seq-profiled cell and tissue types. GATA3, one of our most-enriched TFs at lncRNA promoters and an essential regulator of type 2 helper T-cell (Th2) cytokine production, is itself cis-regulated by an antisense lncRNA (GATA3-AS1), which is increased in patients with allergic rhinitis, a Th2-associated disease [64]. More recently, evidence for large-scale GATA3 regulation of lncRNAs associated with Th2 functions has emerged, and an lncRNA was assigned into a GATA3-containing regulatory network in Th2 cells [65]. Our results support large-scale regulation of lncRNA transcription programs by GATA3, and enhance the list of lncRNAs whose promoters may comprise GATA3 targets.
