Our lab is interested in the epigenetic regulation of chromatin and transcription. Epigenetics is termed as heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying DNA sequence. One of the mechanisms is through covalent post-translational modifications-such as methylation-of histones that wound by DNA to form chromatin in the eukaryotic cells. Histone methylation is dynamically regulated by enzymes, namely lysine methyltransferase (KMT) and lysine demethylase (KDM), that add and remove the methyl marks, respectively. These histone methyl marks are then recognized by “reader” domains or proteins, which in turn dictate the “on” or “off” states of the underlying genes. We have previously identified the Plant HomeoDomain (PHD finger) as a novel reader of methylated histones. There are more than 200 PHD fingers in the human proteome. Currently we are focusing on elucidating the roles of the PHD fingers present in the recently identified JmjC domain-containing KDMs in the regulation of chromatin dynamics. Recently we developed a histone peptide array for a high-throughput screen to identify novel reader proteins that recognize distinct histone methylation.
We are also interested in understanding the broader roles of KMTs and KDMs in modulating not only histones, but also non-histone proteins in a variety of biological processes and disease models, with the focus on breast cancer, cancer stem cells and mouse embryonic stem cells. We employ a combination of approaches including conventional biochemistry, molecular and cellular biology as well as the cutting-edge high-throughput sequencing technology (ChIP-seq and RNA-seq) to address these questions. Our long-term goal is to understand the molecular mechanisms of epigenetic regulation during normal development, and how disruption of the chromatin homeostasis leads to pathological development.