Abstract
Transcription in animal cells is executed by multi-subunit RNA polymerases and complex arrays of cognate initiation factors (the general transcription machinery). In the case of RNA polymerase II, which transcribes genes’ encoding proteins, the function of these factors on specific genes is regulated by gene- and cell-specific DNA binding factors that act in conjunction with diverse co-activators and co-repressors. These cofactors include both chromatin remodeling/histone modifying factors (e.g. the p300/CBP histone acetyl-transferases and the SET1/MLL H3K4 methyl-transferases) and other factors (e.g. Mediator, TBP-associated factors) that facilitate more direct communication between enhancer-bound regulatory factors and the general transcription machinery. Emphasizing biochemical studies with cell-free systems reconstituted with recombinant chromatin templates and purified transcription factors, as well as cell-based and genetic analyses, the cooperative functions and mechanism of action of various co-activators will be discussed in relation to gene regulation by selected transcriptional activators that include the tumor suppressor p53, nuclear hormone receptors, and leukemic fusion proteins.
About the speaker
Prof Robert G Roeder received his PhD in Biochemistry from the University of Washington in 1969. He joined the Washington University in St Louis as an Assistant Professor in 1971 and moved to the Rockefeller University in 1982. He is currently the Arnold and Mabel Beckman Professor and Head of the Laboratory of Biochemistry and Molecular Biology.
Prof Roeder has pioneered biochemical studies of transcriptional regulatory mechanisms that have led to both the discovery and the functional and mechanistic characterization of nuclear RNA polymerases (I, II, and III), cognate classes of RNA polymerase-specific initiation factors, the first of several thousand gene- and cell-specific transcriptional activators, and a variety of ubiquitous and tissue-specific transcriptional co-activators. More recently, his integrated biochemical studies of histone acetyl and methyl transferases in defined cell-free systems have provided formal proof for their function through histone modifications, along with underlying mechanisms, as well as complementary functions in the direct modification of transcription factors. Apart from his elucidation of the most fundamental aspects of transcription processes, Prof Roeder has contributed extensively to our understanding of the function and mechanism of action of gene-specific factors in various normal and pathological biological processes.
Prof Roeder received numerous awards including the Herbert Tabor Research Award by the American Society for Biochemistry and Molecular Biology (2016), the Albert Lasker Basic Medical Research Award (2003), the Canada Gairdner International Award (2000), and the US National Academy of Sciences Award in Molecular Biology (1986). He was also elected an Associate Member of the European Molecular Biology Organization (2003), a Fellow of the American Academy of Arts and Sciences (1995), a Fellow of the American Association for the Advancement of Science (1992) and a member of the US National Academy of Sciences (1988).
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