Critical role of Znhit1 for postnatal heart function and vacuolar cardiomyopathy.

ABSTRACT: Ca2+ is critical for cardiac electrical conduction and contractility, and aberrant Ca2+ homeostasis causes arrhythmia and heart failure. Chromatin remodeling modulates gene expression involved in cardiac sarcomere assembly and postnatal heart function. However, the chromatin-remodeling regulatory mechanism of cardiac Ca2+ homeostasis is unknown. Here, we found that Znhit1, a core subunit of the SRCAP remodeling complex, was essential for heart function. Deletion of Znhit1 in postnatal hearts of mice resulted in arrhythmia, idiopathic vacuolar cardiomyopathy, rapid heart failure, and premature sudden death. In addition, the level of Casq1, a sarcoplasmic reticulum Ca2+ regulatory protein, was massively elevated while SERCA2a showed reduced protein level. Mechanistically, the Znhit1 modulate

SUBMITTER: Shi Y 

PROVIDER: S-EPMC8986070 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature