Cardiac enhancers: Gateway to the regulatory mechanisms of heart regeneration

Abstract

The adult mammalian heart has limited regenerative capacity. Cardiac injury, such as a myocardial infarction (MI), leads to permanent scarring and impaired heart function. In contrast, neonatal mice and zebrafish possess the ability to repair injured hearts. Cardiac regeneration is driven by profound transcriptional changes, which are controlled by gene regulatory elements, such as tissue regeneration enhancer elements (TREEs). Here, we review recent studies on cardiac injury/regeneration enhancers across species. We further explore regulatory mechanisms governing TREE activities and their associated binding regulators. We also discuss the potential of TREE engineering and how these enhancers can be utilized for heart repair. Decoding the regulatory logic of cardiac regeneration enhancers presents a promising avenue for understanding heart regeneration and advancing therapeutic strategies for heart failure.