Steven J. Triezenberg Professor (on leave)
Current position:
Dean of the Graduate School,
Van Andel Institute, Grand Rapids, MI
- B.S. 1979, Calvin College
- Ph.D. 1984, The University of Michigan
- Helen Hay Whitney Postdoctoral Fellow, 1984-87, Carnegie Institution of Washington
- MSU Teacher-Scholar Award, 1993
- NIH Research Career Development Award, 1994-99
- Distinguished Faculty Award, College of Human Medicine, 1996
Van Andel Institute
333 Bostwick. N.E.
Grand Rapids, MI 49503
Office: 616-234-5704
Lab: 616-234-5109
Publication search:
Steven J. Triezenberg Research Interests
The question that drives the research in this laboratory is how the expression of genes in eukaryotic cells is regulated. In particular, we focus on the mechanisms whereby transcription of protein-encoding genes (that is, the synthesis of mRNA) is activated by a regulatory protein.
One model system for much of our work utilizes a transcriptional activator protein from herpes simplex virus, a nearly ubiquitous human pathogen. This activator, termed VP16, stimulates transcription of the first viral genes to be expressed during an infection, and thus triggers the entire cascade of viral gene expression and replication that eventually leads to the production and release of new virus. The transcriptional activation domain of VP16 is exceptionally potent, can function when fused to many other DNA-binding proteins, and is capable of activating transcription in mammalian, yeast, insect, and plant cells. This versatility and potency has made VP16 an important model for many investigations into mechanisms of transcriptional activation.
To explore the structure and function of the VP16 activation domain, we have generated many mutations throughout this domain and have tested the altered proteins in genetic and biochemical assays of transcription. Among the surprising results of our work are the observations that this domain actually comprises two subdomains, each capable of independent activity. These two subdomains seem to function by distinct mechanisms, including preferences for different kinds of core gene promoters. Although VP16 and other activators are rich in acidic amino acids, the most important residues are hydrophobic or aromatic amino acids. The structure of this domain is quite flexible until it interacts with its target proteins as part of the mechanism of activation. A surprising number of such target proteins have been identified, including basal transcription factors and co-activator or adaptor proteins. These discoveries have significant implications for models of transcriptional regulation in general and for the potential of VP16 as a target for antiviral therapy.
In collaboration with MSU colleague Mike Thomashow, we have begun to explore one mechanism of transcriptional activation in plants. The expression of certain genes is induced when plants encounter cold temperatures, as one aspect of the protective mechanism termed cold acclimation. When a transcription factor involved in this genetic switch was introduced into yeast cells, its activity depended on a complex of proteins termed transcriptional adaptors (initially identified in yeast experiments performed with VP16!). One function of this adaptor complex is to acetylate histones and thereby to relieve the repression of transcription caused by packaging DNA into chromatin. We have now isolated genes encoding several transcriptional adaptor proteins from the model plant organism Arabidopsis, and are launching molecular genetic and biochemical studies of the role of histone acetylation by these proteins during plant gene expression.