|Address:||Kaul Human Genetics Building
720 20th Street South
Birmingham, AL 35294-0024
In eukaryotic cells, DNA is packaged with histones to form chromatin. Once thought merely as a static structure for DNA compaction, chromatin has now been recognized as being highly dynamic and plays vital regulatory roles in almost all nuclear processes including transcription, replication, repair, recombination, and chromosome segregation. Research during the last ten years revealed that two kinds of activities contribute to chromatin fluidity. One is ATP-dependent nucleosome remodeling; the other is covalent modifications of histone tails. Our lab is particularly interested in how covalent modifications of histone tails regulates chromatin function.
Mostly on its N- and C- terminal tails, histones can be covalently modified by acetylation, phosphorylation, methylation, ubiquitination and ADP-ribosylation. Different modifications control different physiological processes. Acetylation plays fundamental roles in transcription regulation. Methylation, depending on the methylation sites and status, modulates a variety of biological processes including transcription, heterochromatin formation, DNA methylation, Gene imprinting, and X chromosome inactivation. The role of histone ubiquitination has just been revealed. We have been focusing our research on two of those modifications: methylation and ubiquitination.
We will take a series of steps to elucidate the functions of these modifications. First, we will identify novel enzymes responsible for those modifications; second, we will explore functions of those modifications on chromatin-based processes such as transcription; finally we will try to understand the mechanism of those modifications on transcription and further investigate the biological consequences of these modifications. Our long-term goal is to apply this basic research for human diseases.
When I was a postdoc in Dr. Yi Zhang’s lab, my colleagues and I used unique biochemical approaches to address these questions. We have successfully identified six novel HMTases (PRMT1, SET7, SET8, ESET, EZH2, and hDOT1), and more recently, one histone H2A ubiquitin ligase (hPRC1L). I will continue to investigate the biological roles of these enzymes in vivo to gain a better understanding of how the deregulation of these enzymes relates to dysfunction of cell proliferation and human diseases such as cancer. Our preliminary studies show that several of these HMTases play important roles in cancer development.
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. Then he 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 UAB in 2004.