Max Planck Research Group
High-Resolution Functional Genomics
Introduction & Scope of our research
Gene transcription, the process where nascent RNA is synthesized along chromatin DNA by RNA polymerase, represents a major target for regulating cell function and also underlies cell growth and differentiation.
The key enzyme that pervasively transcribes eukaryotic genomes and that gives rise to all protein-coding and many non-coding RNAs of a cell is RNA polymerase II (Pol II). For decades it was thought that Pol II transcription is predominantly regulated during initiation. However, recent advances in sequencing techniques that provide a quantitative measure of nascent RNA and that allow the genomic localization of RNA polymerases at nucleotide resolution have now challenged this longstanding view. These high-resolution genomic approaches have not only uncovered new transcriptional activities –the functions of which are unknown- but also revealed wide-spread transcriptional pausing of Pol II during transcription elongation and termination suggesting that these later stages of nascent transcription pose major hubs for gene regulation. The molecular mechanisms that underlie these post-initiation regulatory events are poorly defined and their role during cell differentiation remains unexplored.
The goal of our research
The primary goal of our research is to reveal the key mechanisms that underlie the regulation of chromatin-mediated nascent RNA polymerase II transcription in differentiated mammalian cells and during cell differentiation. Specifically, we aim to understand how post-initiation regulatory events are established in a dynamic chromatin environment in vivo and how these regulatory mechanisms control and coordinate cellular differentiation. We are also interested in how a dysregulation of nascent transcription causes human diseases.
We are addressing these fundamental questions by an interdisciplinary combination of high-resolution genome-wide approaches, genome engineering techniques, genetics experiments and bioinformatics tools. We are also developing new quantitative methods to investigate the molecular mechanisms that drive nascent transcription in mammalian cells.