Examine the effects of promoter sequences and enhancer priming on transcriptional coordination
How do promoters influence transcriptional bursts?
Using quantitative live imaging, genetic manipulation and mathematical modeling, we can decode how core promoter motifs regulate key rate-limiting steps of transcription in the early Drosophila embryo. Applying a novel machine learning approach, we discovered TATA box-driven promoters can be recapitulated by a simple two state model with an inactive OFF and permissive ON from which Pol II initiates transcription. Loss of the TATA motif reduces the ON state duration. The Initiator (INR) promoter motif, in contrast, is associated with a three state model consisting of a permissive ON, OFF1 (on the order of seconds) and OFF2 (on the order of minutes). This long, infrequent OFF2 state is associated with Pol II pausing, but under a model where only a subset of polymerases are stably paused.
Our goal is to understand the genetic and molecular mechanisms underlying promoter state transitions during the maternal-to-zygotic transition.
Pimmett*, Dejean* et al., in press at Nature Communications.