Structural biology laboratory of Epigenetics

In eukaryotic cells, DNA is hierarchically packaged into a higher order structure called chromatin. Chromatin is a dynamic structure built of smaller, more fundamental units called nucleosome, which is the target of epigenetic regulation. Nucleosomes are modified in several ways by a host of multi-subunit protein complexes. Despite the relative abundance of published structural and biochemical works on epigenetic gene regulators, most studies are limited to looking at individual subunits or even individual domains from these large multi-protein complexes and their interactions with histone tails. In the interest of gaining a better understanding the molecular mechanisms of epigenetic gene regulation, we will focus on investigating the molecular mechanisms of nucleosome assembly, modification and recognitions by the multi- protein complexes rather individual subunit. To achieve these goals, we are using an integrative structural biology approach to obtain structures for these large complexes as they interact with nucleosomes. When we obtain these structures, we will use both in vitro and in vivo approaches to study the way each complex and its subunits affect nucleosomes. We expect the outcomes of this research will provide exciting insight into the molecular mechanisms of epigenetic gene regulation. They will also help us establish a platform upon which to develop and even cure diseases caused by defects in epigenetic gene regulation. Alzheimer’s (AD), Parkinson’s (PD), Spinocerebellar Ataxia (SCA), and Huntington’s (HD) disease are among the most common neurodegenerative diseases. HD and SCA belong to the polyglutamine (polyQ) disease family. PolyQ diseases are dominantly inherited neurodegenerative disorders that typically manifest in midlife. They include motor, psyc