||Tapas K. Kundu, Professor
Molecular Biology & Genetics Unit, Jawaharial Nehru Centre for Advanced Scientific Research (JNCASR),Bangalore,India.
|| Eukaryotic genome is organized into a highly dynamic nucleoprotein structure referred to as chromatin. The fundamental unit of chromatin is a nucleosome, comprising of around 200 base pairs of DNA and four different core histones. The epigenetic modification of DNA and core histones fine-tune the genome function, thereby serving as a fundamental regulator of cellular homeostasis, in physiological as well as pathophysiological conditions.
Reversible acetylation of histone and non-histone protein is one of the most well studied epigenetic modifications in the context of disease. Targeting the enzymatic system involve in this process has proved to be a promising therapeutic approach, since a few small molecules have already been approved as drugs. We have discovered several small molecule inhibitors of histone acetyltransferases and in an experimental system have established their therapeutic potential in treating cancer and AIDS. Our
laboratory has discovered the first know small molecule, specific activator of the acetyltransferase KAT3 family (p300/CBP). We have shown that this activator can induce neurogenesis in the mouse brain and thereby enhance the formation of long term memory. Recently these molecules have also been shown to effectively revert the memory in ‘Alzheimer’s’ mouse model. The effectiveness of this class of molecules is currently being studied in the process of neurogenesis and depression.