Robert G. Roeder - Major Discoveries

Major Discoveries

• 1969-1977: In 1969, as a graduate student at the University of Washington, Roeder discovers that three enzymes, called RNA polymerases, directly copy DNA in animal cells. As a professor at Washington University in St. Louis, he goes on to show that these enzymes, referred to as Pol I, II and III, recognize and copy distinct classes of genes.

• 1977-1979: Roeder develops cell-free systems to better study transcription. Composed of the purified RNA polymerases and components extracted from cell nuclei, the systems allow researchers to recreate transcription in a test tube in a way that faithfully mimics the real process in cells.

• 1980: The development of cell-free systems leads to the identification of complex sets of proteins called accessory factors that are essential for each individual RNA polymerase (e.g., TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH for Pol II, and TFIIIB and TFIIIC for Pol III) to "read" specific target genes.

• 1980: Roeder identifies the first mammalian gene-specific activator, called TFIIIA. TFIIIA and similar proteins bind to specific DNA sequences and enhance the reading of corresponding target genes. Repressors perform the opposite task by inhibiting a gene's activity.

• 1990s: A decade of research culminates with the discovery of coactivators, large protein complexes that provide a bridge between the activators and repressors and the RNA polymerases and other components of the general transcription machinery.

• 1992: Roeder's laboratory demonstrates that coactivators can be ubiquitous, monitoring many genes in a variety of cells, or specific to one particular cell type. Roeder and colleagues introduce the concept of cell specificity after they demonstrate that the coactivator OCA-B, the first cell-specific coactivator, discovered by Roeder in 1992, is unique to immune system B cells.

• 1996: Roeder's laboratory discovers the major conduit for communication between gene-specific activators and the general transcription machinery in animal cells: a giant coactivator (TRAP/SMCC) that consists of about 25 different protein chains and is referred to as the human mediator after its counterpart in yeast.

• 2002: Roeder and colleagues show that a single component of the mediator is essential for the formation of fat cells — a finding that may one day contribute to new treatments for diabetes, heart disease, cancer and other conditions in which the fat-making process breaks down.