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Daria Shlyueva shows the way to the identification of signal-dependent enhancers for different pathways

Daria Shlyueva a PhD Student in the Stark lab at IMP is the first author of a paper published today in Molecular Cell, showing how genome-wide quantitative hormone-responsive enhancer-activity maps can be obtained.  This approach is extremely versatile and can be applicable to study enhancers in diverse signaling pathways.

In 2012 Cosmas Arnold, a VBC PhD Alumni from the Stark lab, developed STARR-seq, an activity-based enhancer screening method.  Using this powerful approach Daria screened for enhancers that respond to hormone treatment. She treated two Drosophila melanogaster cell types with the hormone ecdysone and identified hundreds of hormone-responsive enhancers. This allowed Daria to thoroughly analyse the features of the enhancer DNA sequences. Surprisingly Daria found that besides the expected ecdysone receptor motifs, the enhancer sequences were enriched in other motifs, moreover, these motifs are cell-type-specific.

Previous studies screened for enhancers by looking at the hormone receptors and other DNA-binding proteins, here for the first time, the unbiased approach developed by the Stark lab allowed the identification of regulatory sequences without prior knowledge of the transcription factors acting downstream of a signaling pathway. The combination of different genome-wide methods also allowed Daria to conclude that some enhancers are not accessible before hormone treatment, in contrast to previous studies. Daria’s results advise that one cannot assume enhancer function just by looking at chromatin structure or transcription factors binding. 

This is another remarkable achievement by a VBC PhD Student. According to Daria her main realization was, with the support from the Stark group (which combines wet lab and bioinformatics expertise), learning how to and analyzing her own data!

“The best thing about working at the VBC is the freedom you have to test different hypothesis. In this paper we used all high-throughput methods available, and the generation of data was not the bottleneck. The challenge was the data analysis” (Daria Shlyueva)

Daria has a BSc. in Medical Biophysics from the St.Petersburg State Polytechnic University (Russia). She then moved to Sweden for a M.Sc. in Biomedicine at the Karolinska Institute. In 2010 she joined the VBC PhD Programme to work with Alex Stark at the IMP. Daria is now preparing her PhD defence and will then apply for a postdoc.

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Shlyueva D, Stelzer C, Gerlach D, Yáñez-Cuna JO, Rath M, Boryn LM, Arnold CD, Stark A (2014) Hormone-Responsive Enhancer-Activity Maps Reveal Predictive Motifs, Indirect Repression, and Targeting of Closed Chromatin. Mol Cell, Available online 27 March 2014, 10.1016/j.molcel.2014.02.026