Systems biology of regulatory motifs and networks – towards understanding gene expression from the DNA sequence
The regulation of gene expression in response to developmental or environmental stimuli is a crucial mechanism in all organisms. Transcription is regulated by trans-acting transcription factors that recognize cis-regulatory DNA elements (CRMs or enhancers), and function in a combinatorial fashion. Enhancers retain their activity even when placed in artificial contexts (such as in reporter gene assays), but the exact requirements for enhancer function, i.e. a regulatory code, remain unknown. Enhancer activity cannot be predicted from the DNA sequence. Employing an interdisciplinary approach, we use both bioinformatics and molecular-biology-based methods to achieve a systematic understanding of the structure and function of enhancers. Our goal is to “crack” the regulatory code, predict enhancer activity from the DNA sequence, and understand how transcriptional networks define cellular and developmental programs.
- Arnold, CD., Zabidi, MA., Pagani, M., Rath, M., Schernhuber, K., Kazmar, T., Stark, A. (2016). Genome-wide assessment of sequence-intrinsic enhancer responsiveness at single-base-pair resolution. Nat Biotechnol. (abstract)
- Stampfel, G., Kazmar, T., Frank, O., Wienerroither, S., Reiter, F., Stark, A. (2015). Transcriptional regulators form diverse groups with context-dependent regulatory functions. Nature. 528(7580):147-51 (abstract)
- Zabidi, MA., Arnold, CD., Schernhuber, K., Pagani, M., Rath, M., Frank, O., Stark, A. (2015). Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature. 518(7540):556-9 (abstract)
- Kvon, EZ., Kazmar, T., Stampfel, G., Yáñez-Cuna, JO., Pagani, M., Schernhuber, K., Dickson, BJ., Stark, A. (2014). Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature. 512(7512):91-5 (abstract)
- Arnold, CD., Gerlach, D., Stelzer, C., Boryń, ŁM., Rath, M., Stark, A. (2013). Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science. 339(6123):1074-7 (abstract)