What is Transcription? Who is studying it at MSU?

Transcription is the process by which the enzyme RNA polymerase makes copies of genes in the form of RNA, allowing the information encoded in the DNA to be "expressed". Transcription is a highly regulated process, representing the initial control of the flow of genetic information. Transcriptional regulation underlies much of development, physiological responses, and cancer. The mechanisms by which RNA polymerase activity is controlled is a central concern of biological research today. Transcription is controlled by proximal and distal regulatory sequences in the DNA which recruit transcription factors to a gene. Basal transcription factors are thought to participate in the transcription of most genes, while regulatory factors control transcription in a promoter-specific fashion.

In prokaryotes, transcription is carried out by a single type of RNA polymerase or "core" enzyme. The promoter specificity of RNA polymerase can be altered by different types of sigma factors, which bind to the core enzyme to form a "holoenzyme". LEE KROOS and colleagues are studying the role of sigma factors in during the development of the soil bacterium, Bacillus subtilis and control of transcriptional regulators in Myxococcus xanthus.

In eukaryotes, most protein-coding genes are transcribed by RNA polymerase II (Pol II). A number of basal transcription factors are involved in controlling this enzyme's function at the level of initiation, elongation and termination. One of these factors, TFIIF, plays a role in recruiting Pol II to the promoter and stimulates transcriptional elongation. ZACH BURTON'S lab is employing biochemical techniques to learn how TFIIF functions. JIM GEIGER is using X-ray crystallography to characterize the structure of transcription factors bound to the promoter. Bill Henry's lab is studying the machinery involvedin expression of small nuclear RWA genes, controlled by RNA PolII and PolIII

Activators and repressors are factors which stimulate or decrease transcription of genes through interaction with the core transcriptional machinery. STEVE TRIEZENBERG and colleagues are utilizing biochemical assays and yeast genetics to understand how the viral protein VP16 stimulates transcription. In DAVID ARNOSTI'S lab, transcriptional repressor proteins from Drosophila are being analyzed in transgenic organisms and in vitro to determine how these proteins act as developmental "switches" to regulate gene expression. Chromatin modification is one of the central points at which eukaryotic genes are regulated, and projects in MIN-HAO KUO'S, Steve Triezenberg's and JONATHAN WALTON'S laboratories are focused on th enzymes that control this process.

Viral gene expression is regulated by cellular transcription factors; MICHELE FLUCK and colleagues are studying the role of enhancer sequences and the factors that bind them in polyoma virus, a mouse model system for breast cancer. The estrogen receptor (ER) is a transcription factor also implicated in breast cancer; RICHARD MIKSICEK is analyzing the roles of alternative splice forms of ER in cancer cells.

Transcriptional regulation is an important aspect of the field of toxicology. JAY GOODMAN is testing the hypothesis that hypomethylation of DNA is an epigenetic, nongenotoxic, mechanism underlying the aberrant expression of oncogenes involved in carcinogenesis. TIM ZACHEREWSKI and colleagues are studying the role of transcription factors in modulating the effects of dioxin on gene expression.

KARL OLSON focuses on the mechanisms by which blood glucose levels affect the transcription of the insulin gene in pancreatic cells, and has identified limiting factors which are responsible for glucose resistance in a diabetes model system.

Physiological responses to environmental changes are also important in plant biology; MICHAEL THOMASHOW's and colleagues have utilized a genetic approach to identify genes important for regulation of genes conferring cold resistance; one of these genes is homologous to a coactivator important for VP16 activity (see Triezenberg, above).

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