Defining the Role of Epigenetic Regulation in Normal and Pathological Development. Epigenetics, the mechanism that defines gene expression pattern without changing DNA sequences, provides cells with transcriptional memory to allow the transmission of gene expression patterns during cell division, and with developmental flexibility to permit reprogramming of gene expression patterns during embryogenesis. The far-reaching consequences of epigenetics on normal development and pathological conditions have recently been demonstrated in many model systems and in multiple biological processes, including but not limited to cell fate determination, maintenance of tissue differentiation, and cancer occurrence.
Recent studies have highlighted the importance of chromatin and its modifications in epigenetic regulation. Our laboratory has focused on two forms of histone modification, methylation and ubiquitination. Using an unbiased biochemical approach starting with over 2,000 liters of HeLa cells, we have identified several key enzymes that are responsible for site-specific histone methylation. We further revealed that methylation of histones on different residues plays crucial and previously undefined functions in transcriptional regulation, DNA damage repair, and X chromosome inactivation. These studies contribute significantly to our current understanding of histone methylation in transcriptional control and chromatin regulation and help to define the molecular basis for epigenetic regulation of gene expression.
Current work in the laboratory focuses on histone ubiquitination. By studying H2A ubiquitination, we have solved the thirty-year puzzle of H2A ubiquitination by defining the enzyme for H2A ubiquitination and revealing the intriguing link between H2A ubiquitination and PcG protein-mediated gene silencing. Recently, we have identified the deubiquitinase for histone H2A and demonstrated that H2A deubiquitination controls cell cycle progression and gene expression. In addition, we have for the first time detected H3 and H4 ubiquitination, and demonstrated that this process facilitates cellular responses to DNA damage. We are employing a combination of biochemical and genetic approaches to decipher the functions of these histone modifying enzymes in stem cell pluripotency, cancer development, and cell fate determination. The long-term goal of these studies is to apply knowledge derived from basic science to improve human health.
Dr. Hengbin Wang (b.1969) is an Assistant Professor of Biochemistry and Molecular Genetics. Dr. Wang received his B.S. degree from Hebei Normal University (1991) and Ph.D. degree from China Agricultural University (1997) in China. He began his first postdoctoral training in Kyushu University, Japan. He then moved to the University of North Carolina at Chapel Hill, joining Dr. Yi Zhang's laboratory to study the roles of histone modifications in regulating chromatin functions. He joined the UAB faculty in 2004.