Cardiac ventricular chambers are epigenetically distinguishable

The left and right ventricles are muscular chambers of the heart that differ significantly in the extent of pressure workload. The regional and differential distribution of gene expression patterns is critical not only for heart development, but, also in the establishment of cardiac hypertrophy phenotypes. The cells of the myocardium employ elaborate regulatory mechanisms to establish changes in chromatin structure and function, yet, the role of epigenetic modifications and specific gene expression patterns in cardiac ventricles remains poorly understood. We have examined gene expression changes and studied histone H3 and H4 acetylation as well as dimethylation of lysine 4 on histone H3 on promoters of α-Myosin heavy chain gene (α-MHC), β-Myosin heavy chain gene (β-MHC), Atrial natriuretic peptide gene (ANp), B-type natriuretic peptide gene (BNp) and Sarcoplasmic reticulum Ca(2+) ATPase gene (SeRCA2a). The recruitment of histone acetyltransferase (HAT) enzyme p300, which is a transcriptional coactivator, was also studied on the hyperacetylated promoters using immunopurification of soluble chromatin in the left and right ventricles of the mouse. We present evidence for the first time that the pattern of gene expression is closely linked with histone modifications and propose the left and right chambers of the heart are epigenetically distinguishable.