At least one of the SRB subunits is a direct target of the GAL4 transcriptional activator. Other components of the subcomplex have been implicated in chromatin remodeling during transcription initiation. Further genetic and biochemical study of the holoenzyme and its SRB complex should lead to additional insights into the molecular mechanisms involved in the regulation of transcription initiation. We recently isolated a human homologue of the yeast SRB7 gene and used it to facilitate purification characterization of a mammalian RNA polymerase II holoenzyme. The isolation and characterization of the mammalian SRB subcomplex is currently underway.
Macrophage are frequently the first line of immune defense against infection.
Mycobacterial diseases are among the oldest infectious diseases described, and they remain among the most important causes of human morbidity and mortality worldwide. For example, the World Health Organization estimates that one-third of all humans are currently infected with Mycobacterium tuberculosis . HIV is the cause of the more recent AIDS epidemic, and many important questions remain to be answered about HIV pathogenesis. One of our goals is to better understand the interaction between these pathogens and their host cells, and another is to develop new tools for disease prophylaxis and therapy. We are investigating the changes in gene expression exhibited by macrophage after infection by M. tuberculosis , and have recently discovered that mycobacterial infection induces the expression of a novel cytokine called osteopontin.