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

Yifei Miao, Nassim E. Ajami, Tse-Shun Huang, Feng-Mao Lin, Chih-Hong Lou, Yun-Ting Wang, Shuai Li, Jian Kang, Hannah Munkacsi, Mano R. Maurya, Shakti Gupta, Shu Chien (), Shankar Subramaniam () and Zhen Chen ()
Additional contact information
Yifei Miao: Beckman Research Institute, City of Hope
Nassim E. Ajami: University of California at San Diego
Tse-Shun Huang: University of California at San Diego
Feng-Mao Lin: Beckman Research Institute, City of Hope
Chih-Hong Lou: Beckman Research Institute, City of Hope
Yun-Ting Wang: Beckman Research Institute, City of Hope
Shuai Li: University of California at San Diego
Jian Kang: University of California at San Diego
Hannah Munkacsi: Beckman Research Institute, City of Hope
Mano R. Maurya: University of California at San Diego
Shakti Gupta: University of California at San Diego
Shu Chien: University of California at San Diego
Shankar Subramaniam: University of California at San Diego
Zhen Chen: Beckman Research Institute, City of Hope

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02113-y

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