Fig. 8.

Schematic illustration of LEENE–eNOS regulatory mechanism. The LEENE-associated enhancer (located in chr14) forms proximity association with eNOS locus (in chr7) under both static/basal/control (ctrl) (a) and stimulated conditions (PS or statins) (b), but is at a higher probability in the latter condition. In both conditions, KLF2 and KLF4 transcriptionally regulate LEENE and eNOS through binding to TFBS in the promoters of both genes. The LEENE RNA transcripts serve as guides to facilitate RNA Pol II binding to the promoter of eNOS. This enhancer lncRNA-mediated transcriptional regulation positively modulates the nascent eNOS mRNA synthesis to promote endothelial function