The yin and yang of YY1 in cardiovascular health and disease.

Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor of the GLI-Krüppel family, known for its multifunctional and context-dependent roles in gene regulation. YY1 can function as both a transcriptional activator and repressor, making it a key regulator in various physiological and pathological processes. Emerging evidence highlights its importance in the cardiovascular system, where it contributes to blood vessel formation, heart development, and blood pressure regulation. YY1 has also been implicated in cardiovascular diseases, such as atherosclerosis, hypertension, dilated cardiomyopathy, myocardial infarction, and heart failure. Mechanistically, YY1 exerts its dual regulatory functions through its canonical DNA-binding transcriptional activity and its role in chromatin remodeling within cardiovascular cells. Furthermore, recent studies show YY1 shapes the epitranscriptome in vascular smooth muscle cells by controlling the expression of the m6A writer METTL3, expanding its influence over epigenomic regulation of gene expression. This review summarizes the latest research on YY1's roles in vascular and cardiac biology, emphasizing its contributions to cardiovascular health and disease. We highlight its activating and repressing functions in diverse vascular and cardiac contexts, illustrate mechanisms underlying its dual roles, and propose YY1 as a context-specific regulator and promoting therapeutic target in cardiovascular medicine.