Effect of cardiomyocyte-specific activation of nuclear receptor subfamily 4 group A member 2 (NR4A2) on poly(A) RNA expression profile in the mouse heart [RNA-seq]

Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a widely expressed immediate early gene induced by a host of physiological signals such as growth factors, cytokines, and neurotransmitters. In the adult mammalian heart, including in cardiomyocytes, NR4A2 mRNAs increase more than 60-fold in response to beta-adrenergic stimulation. However, the nature of the transcriptional remodeling induced by NR4A2 in the stressed heart has remained poorly investigated. We show here that NR4A2 activation in mouse cardiomyocytes profoundly alters the sub-transcriptomes controlling metabolic pathways and calcium transients in the heart. At the metabolic level, NR4A2 induced the expression of glycolytic enzymes while simultaneously down-regulating fatty acid oxidation. Increased NR4A2 expression was also associated with the repression of several genes critical for t-tubules formation, dyads organization, and calcium flux. The findings shed light on a novel regulatory mechanism controlling cardiac homeostasis, and establish a framework to investigate further the roles played by NR4A2 in fetal reprogramming of the adult mammalian heart under various stress conditions.