Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function.

Area of Science:

• Molecular Biology
• Genetics
• Cardiovascular Research

Background:

• Endothelial nitric oxide synthase (eNOS) is critical for vascular homeostasis and function.
• eNOS expression is regulated at multiple levels, but epigenetic mechanisms involving long non-coding RNAs (lncRNAs) are underexplored.

Purpose of the Study:

• To identify and characterize novel epigenetic regulators of eNOS expression.
• To elucidate the role of lncRNAs in modulating eNOS and endothelial cell function.

Main Methods:

• RNA-sequencing and chromatin conformation capture (3C) were employed to identify and analyze lncRNAs.
• Gain- and loss-of-function experiments were performed to assess the impact of LEENE on eNOS expression and endothelial cell function.

Main Results:

• An enhancer-associated lncRNA, named LEENE, was identified and shown to be co-regulated with eNOS.
• LEENE enhances eNOS expression by facilitating RNA Polymerase II recruitment to the eNOS promoter, boosting transcription.
• Modulation of LEENE levels directly impacts eNOS expression and endothelial cell function.

Conclusions:

• LEENE represents a novel epigenetic regulator of eNOS, adding a new layer to our understanding of endothelial homeostasis.
• These findings offer new insights into cardiovascular regulation and potential therapeutic targets involving endothelial function.