FMS BIOINFORMATICS & SYSTEMS BIOLOGY SEMINAR SERIES 2014
Bart Deplancke – Swiss Federal Institute of Technology, Lausanne--Thursday 24 April @ 3.30 pm, Dental Lecture Theatre D
This seminar is very relevant for anyone working on transcriptional control. Bart’s lab has developed an impressive microfluidics platform to measure transcription factor binding affinities, and by combining this with other experimental and computational tools he has successfully identified novel central regulators of fundamental processes.
"Systems-based, quantitative analysis of the regulatory network mediating fat cell differentiation"
Adipogenesis is highly relevant both from a medical research perspective and as a prime model of cellular differentiation. In the first part of my talk, I will present my lab’s efforts to examine whether the current adipogenic regulatory model is exhaustive. To this end, we systematically overexpressed individual transcription factors (TFs) in mouse pre-adipocytes and probed their effect on fat cell differentiation. We identified 26 mostly novel pro-adipogenic TFs (out of 734) and established the top candidate ZEB1 as a central regulator of in vitro and in vivo fat cell differentiation, acting by directly targeting the majority of known early and late adipogenic transcriptional regulators. In the second part, I will introduce a novel targeted proteomics method that we developed with the goal of deriving absolute abundance data for TFs-I will show how we used these data together with binding energetics and chromatin state data to formulate a genome-wide DNA binding model for the adipogenic master regulator PPARγ. Interestingly, this model accurately explains the increase in PPARγ binding sites during the final differentiation stage despite a concurrent saturation in PPARγ copy number. In the final part, I will summarize our findings regarding the molecular role of co-repressors during adipogenesis. Specifically, I will show how some of these co-repressors function as gatekeepers within the adipogenic regulatory network as they directly fine-tune the transcription of pro- and anti-adipogenic genes.
Faculty contact: Diego Miranda-Saavedra (email@example.com), ext. 8590
Sponsored by: Panasonic