Mechanisms of transcription regulation in human development and disease
The Taatjes lab seeks to discover molecular mechanisms that control human gene expression, and how transcription and signaling pathways are altered during development and disease. We focus on sequence-specific, DNA-binding transcription factors (TFs) and the Pre-Initiation Complex (PIC), which consists of Mediator, RNA polymerase II (pol II), TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. The PIC controls the activity of the pol II enzyme, which transcribes all protein-coding genes and most non-coding RNAs in the human genome. Within the PIC, the 1.4 MDa Mediator complex, the 1.3 MDa TFIID complex, and the 0.5 MDa TFIIH complex help regulate pol II activity in ways that remain poorly understood. At a basic level, TFIIH regulates transcription initiation and post-initiation steps (e.g. RNA processing), whereas Mediator and TFIID function by converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). We utilize a variety of experimental techniques that include biochemical, biophysical, molecular and cell biology approaches, as well as metabolomics, proteomics, and transcriptomics.