MAMMALIAN mRNA TRANSCRIPTION AND ITS REGULATION:
Controlling gene expression is essential to growth, development, and sustained life. A critical control point for regulating gene expression is at the level of transcription. The proper regulation of transcription is essential for maintaining normal pathways of cell growth and differentiation, thereby avoiding the rampant cell proliferation observed in tumors. Transcription of protein encoding genes in eukaryotes is orchestrated by a host of protein factors, including RNA polymerase II, general transcription factors (TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), coactivators, chromatin remodeling factors, and gene-specific transcriptional regulators (activators and repressors). The underlying goal of our work is to uncover molecular mechanisms governing mammalian RNA polymerase II transcription. To this end, we use a combination of biochemistry, molecular biology, and molecular genetics to investigate mechanisms of transcriptional regulation in three lines model systems.
Regulation of RNA Polymerase II by non-coding RNAs
In response to heat shock, cells execute a program of gene-specific transcriptional activation and repression. We have found that during the heat shock response in mouse cells, a small non-coding RNA polymerase III transcript, B2 RNA, associates with RNA polymerase II and represses transcription of specific mRNA genes. . . . . -more-
Regulation of Transcription at the Human Interleukin-2 Gene
The mammalian immune system represents a unique model for studying the importance of transcriptional regulation in governing cell growth and differentiation. Studies performed by immunologists have revealed that the development of T-lymphocytes is controlled by the interplay of signal transduction and transcription. Interleukin-2 is a cytokine that acts as an autocrine growth factor promoting the proliferation and development of T cells during the immune response to bacterial and viral infection, as well as tumorigenesis. . . . . -more-
The mechanism of the human RNA polymerase II transcription reaction
A primary goal of our research is to understand the mechanism and regulation of early transcription. The foundation of our studies is a human in vitro transcription system that is reconstituted from highly purified general transcription factors and RNA polymerase II. Using this system, we have developed techniques to experimentally dissect the transcription reaction into 5 steps. . . . -more-