Systems-based, quantitative analysis of the regulatory network mediating fat cell differentiation
Event details
| Date | 28.11.2013 |
| Hour | 12:15 › 13:10 |
| Speaker | Prof. Bart Deplancke |
| Location | |
| Category | Conferences - Seminars |
Adipogenesis is highly relevant both from a medical research perspective and as a prime model of cellular differentiation.
In a 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 a 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.
In a 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 a 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.
Practical information
- Informed public
- Free
Organizer
- Dean's Office, School of Life Sciences
Contact
- Dr H. Hirling / M. Mary