/ Long Noncoding RNA Binds to Primed Proximal Regulatory Regions in Prostate Basal Cells Through a Triplex- and -Mediated Mechanism.

Aside serving as host gene for , transcribes for a chromatin-associated long noncoding RNA (lncRNA) able to restrain the differentiation of prostate basal cells, thus being reannotated as (Long Epithelial -interacting Differentiation-related RNA). We previously showed the presence of sequences in the promoters of genes modulated upon / manipulation. Notably, an element also spans the first and second exons of /, suggesting its possible involvement in target selection/binding. Here, we performed ChIRP-seq to map / chromatin occupancy at genome-wide level in prostate basal cells. Our results confirmed preferential binding to regions proximal to gene transcription start site (TSS). Moreover, enrichment of triplex-forming sequences was found upstream of /-bound genes, peaking at -1,500/-500 bp from TSS. Triplexes formed with one or two putative DNA binding sites within / sequence, located just upstream of the element. Notably, triplex-forming regions of bound genes were themselves enriched in elements. These data suggest, from one side, that triplex formation may be the prevalent mechanism by which / selects and physically interacts with target DNA, from the other that direct or protein-mediated (RNA)/ (DNA) interaction may represent a further functional requirement. We also found that triplex-forming regions were enriched in specific histone modifications, including H3K4me1 in the absence of H3K27ac, H3K4me3 and H3K27me3, indicating that in prostate basal cells / may preferentially bind to primed proximal regulatory elements. This may underscore the need for basal cells to keep / target genes repressed but, at the same time, responsive to differentiation cues.