Expression profiling of yeast cells with mutations in various components of the transcription initiation apparatus has demonstrated that the RNA polymerase II holoenzyme is responsible for transcription of most protein-coding genes and has revealed how genome expression depends on each of the many components of this complex apparatus. It is now possible to envision the development of maps of transcriptional regulatory circuitry in cells. Genome-wide expression analysis with high density DNA arrays has proven to be useful for identifying genes whose expression depends on individual components of the yeast transcription apparatus. The coupling of genome-wide expression analysis using high density DNA arrays with mathematical and computational methods can produce models for transcriptional regulatory networks. Such models can be tested with a combination of genetic and genomic approaches and the molecular mechanisms responsible for the regulation observed in networks can be identified with biochemical and molecular genetic approaches.
Macrophage are frequently the first line of immune defense against infection.
The World Health Organization estimates that one-third of all humans are currently infected with M. tuberculosis. HIV is the cause of the AIDS epidemic, and many important questions remain to be answered about HIV pathogenesis. We would like to know more about the biology of these infectious agents and the macrophage that attempt to control them. Pathogenic microbes have evolved various tactics to undermine and survive host defenses, but the tactics used by Mycobacterium tuberculosis to permit persistent infection in humans are not well understood. To gain insights into infectious disease pathogenesis, the effects of viral and bacterial infection on human macrophage gene expression is being explored with high-density DNA arrays.