This section is interested in transcription factors that regulate the development of the immune system. IRF-8/ICSBP, a DNA specific transcription factor is essential for the development of macrophages and dendritic cells. In addition to their development, IRF-8 controls the expression of interferons and the IL-12 cytokine in these cells, thereby playing a critical role in the establishment of innate immunity. To address the mechanism of IRF-8 action, we performed photobleaching experiments. We show that IRF-8 is moving rapidly in the nucleus and scanning the entire genome by transiently binding to chromatin in macrophages and DCs. Further analysis showed that IRF-8 chromatin interactions are regulated by external cytokine signaling. This study opened a new way to study transcription in living immune cells. Another model we investigate deals with a bromodomain protein Brd4. This protein binds to acetylated chromatin and associates with chromosomes during mitosis. Brd4 is thought to play a role in epigenetic memory. We found that Brd4 interacts with P-TEFb, a Cdk9/CyclinT heterodimer that is essential for RNA polymerase II transcriptional elongation. By chromatin immunoprecipitation analysis of the HIV-1LTR reporter, we provided evidence that Brd4 recruits P-TEFb to the promoter to stimulate transcription. These studies have unraveled a previously unknown role for Brd4 in transcription.
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