Genes are activated through recruitment of RNA polymerase II to their promoters or through the release of a promoter-proximal paused RNA polymerase II. The evolutionary selective pressures and functional advantages behind these disparate mechanisms remain poorly understood. Using genomics approaches we have recently discovered that the HIV-1 provirus is rapidly activated in response to ligands from the immune microenvironment through a mechanism of RNA polymerase II recruitment. We have identified a subset of immune genes which behave in a similar manner (here referred to as “HIV-1 like”). We have also devised high-resolution approaches combined with careful data analysis to measure and quantitate the behavior of RNA polymerase II at these genes. We now want to decipher the underlying mechanisms including the roles of chromatin accessibility, epigenetic marks, transcription factor binding and enhancer functions.
References: Shukla et al., manuscript in preparation.