Laboratory Ritwick Sawarkar

A typical metazoan cell expresses only a fraction of all the genes it inherits from the mother cell. How does a cell decide which genes to express? Organisms have evolved sophisticated logical networks, which select genes for expression. An important element in these networks is chromatin that influences the activity of RNA polymerase enzyme complex. Over the past few years, it has been shown that RNA polymerase II (pol II) gets recruited to promoters of several genes, but pauses shortly thereafter. This appears to be a critical rate-limiting step for gene regulation. The precise reasons and consequences of this event, especially in the context of chromatin, remain largely unknown. Furthermore, how misregulation of pol II pausing is instrumental in diseases such as cancer is unexplored. By employing systems biology, genetics and single cell approaches in Drosophila and mammalian systems, we will elucidate the basic principles of the crosstalk between chromatin and RNA pol II pausing.