“Should I Stay or Should I Go?” - The dynamic life of serum response factor (SRF)
An interdisciplinary team composed of our PIs Prof. Christof M. Gebhardt, Prof. Jens Michaelis and their coworkers as well as colleagues from the Institute of Physiological Chemistry (head: Prof. Bernd Knöll) at Ulm University, analyzed the DNA binding behavior of the transcription factor serum response factor (SRF) at single-molecule resolution.
Many genes are regulated by transcription factors. Binding of these proteins to promoter regions of the DNA results either in transcription (“on”) or repression (“off”) of a gene - like an electric switch. The transcription factor SRF mediates expression of immediate early and cytoskeletal genes. Therefore, it plays an important role in cell cycle regulation, apoptosis, cell growth and differentiation.
The study, which has been recently published in Proceedings of the National Academy of Sciences (PNAS), reveals that binding events of the transcription factor SRF to its promoters can be classified into three distinct time periods: short, intermediate, and long. All three populations were found in different cell types (fibroblasts and primary hippocampal neurons of mice), indicating a conserved mechanism. In addition, this new study identified a surprisingly long average residence time (up to 1 minute) for SRF. The chromatin residence time of the transcription factor could even be increased upon cell stimulation. At the same time, the amount of long binding SRF molecules increased when cells were stimulated.
„Our collaborative study contributes to the fundamental knowledge about the activity of transcription factors and gene regulation. This helps to understand the complex and dynamic interactions”, Lisa Hipp, PhD student at the Institute of Physiological Chemistry and first author of the study, explains.
Hipp, Lisa, et al. "Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation." Proceedings of the National Academy of Sciences 116.3 (2019): 880-889.