Mutations in LMNA cause dilated cardiomyopathy characterized by severe cardiac dysfunction and fatal ventricular arrhythmias, referred to as cardiac laminopathy. We recently found that LMNA-chromatin interactions control the expression of key metabolic enzymes, thereby enabling cardiovascular cells to adjust their metabolic needs. Importantly, Lmna-deficiency resulted in alterations of chromatin accessibility coupled to major changes in metabolites that modulate chromatin structure. The objective of the proposed research program is to decipher the role of LMNA in the crosstalk between epigenetics and metabolism in the pathogenesis of cardiac laminopathy.
