Transcriptional responses to nitric oxide are widescale and source-dependent

TL;DR

This study shows that nitric oxide affects thousands of genes in a way that depends on its source, with distinct effects observed from different NO sources.

Contribution

The paper reveals source-dependent, widespread transcriptional effects of NO, mediated by S-nitrosylation and distinct effectors.

Findings

NO from different sources affects up to 10,000 genes in a source-dependent manner.

NOS isoforms and NO donors produce unique and non-overlapping transcriptional responses.

S-nitrosylation is a major mediator of these transcriptional changes.

Abstract

The transcriptomic effects of nitric oxide (NO) have been widely studied across phylogeny. However, while gene expression is canonically altered by NO, general principles have not emerged. Here, we characterize genetic regulation within a single cell type after exposure to NO derived from endogenous or synthetic donor compounds or produced by 3 different NO synthase (NOS) isoforms under basal and activated conditions. Using RNAseq, we uncover distinct, source-dependent effects of NO on as many as ∼10,000 genes mediated largely by S-nitrosylation. NOS enzymes and NO donors each generated unique transcriptional responses. Our data reveal non-overlapping transcriptional responses to NO that are likely mediated by distinct effectors and enzymes and highlight that NO-treated cell systems may undergo a dramatic and widespread transcriptional response.

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