Yi Zhang

The major focus of the Zhang lab has been the identification and characterization of the chromatin modifying enzymes that include: (1) the ATP-dependent nucleosome-remodeling and histone deacetylase complex NuRD; (2) various histone methyltransferases, including PRC2 and hDOT1L; (3) the JmjC-family of histone demethylases; (4) histone H2A ubiquitin E3 ligase PRC1; and (5) the Ten Eleven Translocation (Tet) family of 5-methylcytosine dioxygenases. The general approach of the lab involves biochemical purification and functional characterization of the enzymes in vitro and in cell culture, genomic characterization of their locations and effect on transcriptome, followed by biological characterization in mouse models. These studies have uncovered a role of these enzymes in transcriptional regulation, as well as in cell fate reprogramming and the development of various diseases, such as metabolic syndrome and cancers. In the recent years, the lab has been focused on functional characterization of epigenetic and chromatin modifications in specific biological processes, particularly during mammalian preimplantation development and in the brain reward system. The limited cell numbers in these biological systems prompted us to develop and apply single cell and/or small cell number techniques for genomic, epigenomic and transcriptome profiling. These techniques are very powerful in addressing cell heterogeneity issues facing many biological systems, including early embryos, brain and cancer.