Our laboratory studies transcription from a mechanistic perspective, using the human transcriptional machinery and primarily biochemical approaches. We have recently focused on (i) the processes through which RNA polymerase II (pol II) initiates RNA synthesis and clears the promoter, (ii) the molecular mechanisms involved in transcript elongation, and (iii) the effects of chromatin structure on transcript elongation. All of these aspects of transcription are important checkpoints in the regulation of gene expression in the cell. The ultimate goal of our studies is a better understanding of the control of gene expression. The accurate duplication of the various stages of transcription in test tube systems provides the necessary tools to uncover regulatory mechanisms.
With very few exceptions, all of the cells in our bodies contain the same genetic information within their DNA. However, each cell utilizes only a very specific subset of the roughly 25,000 human genes. Gene expression begins with copying of the DNA information into an RNA messenger intermediate. For this to occur, the RNA synthesis machinery must first find the correct starting point (the promoter) for each gene. Promoter recognition and subsequent transcription of the gene can then occur in spite of the generally tight packaging of the DNA into chromosomes by the chromosomal proteins. We have only a limited understanding of the molecular mechanisms that reveal just the correct subset of genes to the transcriptional machinery in any given cell type. Failure to transcribe the appropriate gene cohort can lead to disease states, such as cancer. Our laboratory uses test tube systems to study the molecular events that that drive promoter recognition and transcription of genes within the context of chromosomes.