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Nat Commun. 2018 Jan 18;9(1):292. doi: 10.1038/s41467-017-02113-y.

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

Author information

1
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA, 91010, USA.
2
Bioinformatics and Systems Biology Graduate Program, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
3
Department of Bioengineering and Institute of Engineering in Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
4
Genome Editing Core, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA, 91010, USA.
5
Department of Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
6
Department of Bioengineering and Institute of Engineering in Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. shuchien@ucsd.edu.
7
Department of Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. shuchien@ucsd.edu.
8
Department of Bioengineering and Institute of Engineering in Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. shankar@ucsd.edu.
9
Departments of Cellular and Molecular Medicine and Computer Science and Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. shankar@ucsd.edu.
10
Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA, 91010, USA. zhenchen@coh.org.

Abstract

The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.

PMID:
29348663
PMCID:
PMC5773557
DOI:
10.1038/s41467-017-02113-y
[Indexed for MEDLINE]
Free PMC Article

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