Seminar in Organic & Biophysical Chemistry

نویسنده

  • Hila Cohen
چکیده

Recent in vitro protein-DNA binding measurements indicate that transcription factors (TFs) are bound with wide range of affinities to different DNA sequences that lack known consensus motifs, thus challenging the classical picture of specific protein-DNA binding. Our group has previously demonstrated that repetitive DNA sequence elements characterized by certain symmetries, statistically affect protein-DNA binding preferences. We term this type of protein-DNA binding as nonconsensus binding. In the course of my Master research work, I showed that nonconsensus protein-DNA binding is a widespread phenomenon that significantly affects protein-DNA binding preferences for hundreds of TFs. In particular, first, using large-scale in vitro protein-DNA binding measurements performed for 115 mouse TFs, I demonstrated that the majority of these TFs (92%) are significantly affected by the nonconsensus effect. Strikingly, I identified that a small fraction of TFs (11%) respond to the symmetries of repetitive DNA sequence elements in an opposite way compared to the majority of TFs (81%). Next, I identified protein sequence signatures that could be responsible for enhanced nonconsensus binding to DNA. In addition, I analyzed new experimental in vitro measurements performed for more than 1000 TFs from different eukaryotic organisms. Strikingly, I identified that DNA binding preferences of the majority of these TFs (92%) are significantly affected by the nonconsensus effect. Overall, my results suggest that nonconsensus TF-DNA binding constitute a new, major layer of transcriptional regulation in eukaryotic genomes.

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تاریخ انتشار 2015