Dissecting dose-dependent transcriptional regulation through epigenome editing and synthetic biology

Dr. Edda Schulz

Precise, quantitative control of gene activity is essential for the diverse physiological processes that sustain human life. The importance of precise gene control is highlighted by the significant proportion of haplo-insufficient and triplo-sensitive genes. Transcription factors are overrepresented among these dose-sensitive genes, highlighting the importance of understanding dose sensing in transcriptional control. This project builds on our recently developed CasTuner tool, which enables us to measure dose-response relationships in the mammalian genome. By titrating transcription factors in murine or human pluripotent stem cells, we will assess the functional impact of transcription factor dosage on cell differentiation and target gene expression. To decode the rules governing dose sensitivity, we will combine CasTuner with massively parallel reporter assays to enable us to test a large number of DNA elements for their dose-decoding properties. Thus, by combining several cutting-edge technologies, the project will dissect the principles that govern dose sensitivity in mammalian cells.

For more information, visit the website of the Schulz lab.