"This was the Dark Ages," recalls Roeder. "We didn't have many isolated and characterized genes to work with like we do now." For this research he was honored with the American Chemical Society Eli Lilly Award in Biological Chemistry in 1977.
Nature's secrets revealed in test tube In the late 1970s, Roeder developed cell-free systems that allowed him and others to study the function of individual genes and transcription-related proteins outside of living cells, in effect recreating transcription in a test tube in a way that faithfully mimics the real process in cells. Using this powerful test-tube technique, composed of purified RNA polymerases and components extracted from cell nuclei, Roeder identified distinct sets of proteins, called accessory factors, essential for the individual RNA polymerases to recognize start sites on specific target genes.
Significantly, he simultaneously identified the first gene-specific activator, called TFIIIA, in eukaryotes. TFIIIA and similar proteins bind to specific DNA sequences and enhance the "reading" of corresponding target genes by the appropriate subset of the general transcription machinery. Repressors perform the opposite task by inhibiting a gene's activity.
Hundreds of these transcription activators and repressors subsequently have been identified by Roeder and other scientists, and many more are expected for the regulation of genes during such physiological processes as cell growth and division, hormonal processes, virus infection and tumor growth.
"The challenge we now face is understanding the differential regulation of about 30,000 human genes," says Roeder.
Over the last decade at Rockefeller University, Roeder and his colleagues have identified several coactivators, thereby ushering in a modern age in biology. Says Roeder, "We have uncovered a third layer of complexity in the transcriptio
Contact: Joseph Bonner