Project (Michael Lidschreiber - Kristina Zumer)
Genome transcription and regulation

We are uncovering the molecular mechanisms and systemic principles of genome transcription and regulation using a combination of structural biology with functional genomics and bioinformatics in human cells (http://www.mpinat.mpg.de/cramer). We offer projects that will explore regulation of transcription on a genome-wide scale with “multi-omics” approaches.

We develop the experimental and computational tools to capture nascent RNA synthesis. In particular, we have pioneered transient transcriptome sequencing (TT-seq), a method that enables the measurement of RNA synthesis rates and mapping of dynamic enhancer landscapes in vivo. We have used TT-seq to follow cell differentiation processes and cellular responses to hormones, as well as to investigate transcriptional misregulation in cancer cells. Integrating these data with other genome-wide datasets for "multi-omics" approaches, which are combined with theoretical modeling, enables us to elucidate the essential mechanisms of transcriptional regulation in human cells. In particular, we can determine the length of time that RNA polymerase II pauses at the beginning of genes; the velocity of RNA polymerase II elongation across entire genes and the coupling of pre-mRNA splicing and transcription. Additionally, we utilize CRISPR/Cas9 to engineer cells in which we can rapidly and specifically degrade or inhibit proteins regulating transcription to uncover the molecular roles of essential transcription factors. See the list of our most recent publications below.

We continue to develop and use functional genomics methods and computational approaches to study the molecular mechanisms of gene regulation in differentiation, cell cycle and cell identity. The focus of future projects will be moving from bulk sequencing methods to single molecule scale analyses of transcription kinetics. Work on these projects requires experimentalists (life sciences background) and computational biologists (background in mathematics, informatics etc.) with a strong interest in dissecting molecular mechanisms of transcription and its regulation. Possible projects will be developed together with candidates interested in specific areas.


In our research group we also offer PhD projects in structural biology and in vitro systems:
https://www.uni-goettingen.de/de/application/682457.html





Homepage Research Group
http://www.mpinat.mpg.de/cramer



Publications:

Žumer K, Ochmann M, Aljahani A, Zheenbekova A, Devadas A, Maier KC, Rus P, Neef U, Oudelaar AM, Cramer P: FACT maintains chromatin architecture and thereby stimulates RNA polymerase II pausing during transcription in vivo. Molecular Cell 84 (11), pp. 2053 - 2069.e9 (2024). https://doi.org/10.1016/j.molcel.2024.05.003

Velychko T, Mohammad E, Ferrer-Vicens I, Parfentev I, Werner M, Studniarek C, Schwalb B, Urlaub H, Murphy S, Cramer P, Lidschreiber M: CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release. Molecular Cell 84 (12), pp. 2287 - 2303.e10 (2024). https://doi.org/10.1016/j.molcel.2024.05.007

Xiong L, Tolen EA, Choi J, Velychko S, Caizzi L, Velychko T, Adachi K, MacCarthy CM, Lidschreiber M, Cramer P, Schöler HR: Oct4 differentially regulates chromatin opening and enhancer transcription in pluripotent stem cells. eLife 11, e71533 (2022). https://doi.org/10.7554/eLife.71533

Full publication list: https://www.mpinat.mpg.de/635004/publications