Eric G. described work from the lab uncovering the mechanisms of transcription regulation in Mycobacterium tuberculosis and visited virtually with the biophysics community at Cornell University. Here’s hoping the next visit will be in person!!!
Ankita and other trainees at WashU and SLU presented their science to a broad range of TB researchers. Great job Ankita!
This research was in collaboration with the laboratories of Dylan Taatjes at UC Boulder, Steve Hahn at the Fred Hutchinson Cancer Research Center, and Susan Tsutakawa at LBNL. By comparing the double-stranded DNA processivity of the TFIIH motor subunit involved in transcription initiation, we propose a mechanistic explanation for why different Eukaryotes display distinct start-site usage patterns. Click the image below to go to the paper.
The fitness of an individual bacterial cell is highly dependent upon temporally tuning gene expression levels when subjected to different environmental cues. Kinetic regulation of transcription initiation is a key step in modulating the levels of transcribed genes to promote bacterial survival. The initiation phase encompasses the binding of RNA polymerase (RNAP) to promoter DNA and a series of coupled protein-DNA conformational changes prior to entry into processive elongation. The time required to complete the initiation phase can vary by orders of magnitude and is ultimately dictated by the DNA sequence of the promoter. In this review, we aim to provide the required background to understand how promoter sequence motifs may affect initiation kinetics during promoter recognition and binding, subsequent conformational changes which lead to DNA opening around the transcription start site, and promoter escape. By calculating the steady-state flux of RNA production as a function of these effects, we illustrate that the presence/absence of a consensus promoter motif cannot be used in isolation to make conclusions regarding promoter strength. Instead, the entire series of linked, sequence-dependent structural transitions must be considered holistically. Finally, we describe how individual transcription factors take advantage of the broad distribution of sequence-dependent basal kinetics to either increase or decrease RNA flux.
Ankita gave a great talk describing her recent progress in understanding the possible molecular determinants of DNA repair in Mycobacteria tuberculosis. Stay tuned for more soon!
Drake gave an update to the Biochemistry, Biophysics, and Structural Biology program (@BBSBwustl) on his works in progress.