Hypoxia and HIF-1 suppress SERCA2a expression in embryonic cardiac myocytes through two interdependent hypoxia response elements

► Hypoxia induces downregulation of SERCA2a expression in embryonic cardiomyocytes. ► SERCA downregulation induces specific changes in cardiomyocyte calcium signalling. ► Hypoxia effect on SERCA expression is mediated by HIF-1. ► SERCA2a promoter contains two putative HIF-1 binding HRE-sites. ► HIF-1 binding to both of the HRE-sites is required for expressional suppression.