The CR9 element is a novel mechanical load‐responsive enhancer that regulates natriuretic peptide genes expression

Enhancers regulate gene expressions in a tissue- and pathology-specific manner by altering its activities. Plasma levels of atrial brain natriuretic peptides, encoded the Nppa Nppb, respectively, synthesized predominantly cardiomyocytes, vary depending on severity heart failure. We previously identified noncoding conserved region 9 (CR9) element as putative Nppb enhancer at 22-kb upstream from gene. However, regulatory mechanism remains unknown. Here, we therefore investigated CR9 activation cardiomyocytes using different kinds drugs that induce either cardiac hypertrophy or failure accompanied peptides upregulation. Chronic treatment mice with catecholamines doxorubicin increased activity during progression to failure, which is proportional increases expression. Conversely, for cultured decreased expression, while both. exposing mechanical loads, such stretch hydrostatic pressure, upregulate expression even presence doxorubicin. Furthermore, enhancement loads can be blunted suppressing mechanosensing mechanotransduction pathways, muscle LIM protein (MLP) myosin tension. Finally, showed more robust cell-specific response than −520-bp BNP promoter. concluded novel responds upregulating cardiomyocytes.