Methylation of histone H3 lysine 9 by the Euchromatic Histone Methyl Transferases (EHMT1/2) regulates cardiac myocyte growth and proliferative responses
Heart disease is a leading cause of mortality and morbidity that is increasing with the ageing population. Part of the reason why the heart becomes less healthy during disease and ageing is the loss of the cells that make up the muscle that pumps blood. This is a particular problem following a heart attack (infarction) where up to 1 billion cells may be lost. In other organs of the body such as the liver, this catastrophic loss of cells may not be such a problem because those tissues can regenerate. Heart cells are incapable of dividing and so cannot repair the damaged heart. Instead, heart cells grow (hypertrophy) to make up for the lost muscle. In this way the heart can cope over the short term. However, this growth during disease is ultimately contributes to a decrease in cardiac function and heart failure. For these reasons, the only therapy currently available is transplant. The hypertrophy and inability of adult cardiac myocytes to divide are determined by a change in the number and kind of genes expressed. Our recent research has found how genes involved in regulating cardiac cell divisison and that are involved in disease are switched off in the adult heart. Specifically we find a modification of the proteins around which DNA is wrapped is involved. This is an epigenetic change. In this project, we will aim to test whether this process can be used to increase cardiac myocyte proliferation and prevent the pathological hypertrophic growth of the heart.