Life Sciences Research for Lifelong Health

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Babraham Computational Biology Seminar

Dr Ilyas Yildirim, University of Cambridge


DNA Bending in Transcription Factors and Nucleosomes
The complex architecture of chromatin structure uses nucleosomes as building blocks to package genomic DNA and regulate gene expression. The structure of nucleosome includes a 147 basepair DNA segment wrapped around the surface of histone octamer. Compared to the native B-form conformation of DNA, this tight wrapping creates bending in DNA. Similar to nucleosomes, protein transcription factors, which control the genetic information from DNA to RNA, can also bend DNA through binding. To date, the driving forces that control the bending properties of DNA are unknown. By using the computer technology, it is possible to properly model bending properties of DNA to investigate nucleosome formation in genomic data and properties of transcription factors.

In this talk, I will discuss two systems: 1) CueR/DNA complex, and 2) Nucleosome core particle. In my collaboration with O’Halloran’s Group (Northwestern University), we studied the structural properties of CueR/DNA complex, which is a copper-sensing member of the MerR-family. In the metal-free (repressor) form of CueR, DNA displays a B-form-like conformation. In the metal-bound (activator) form of CueR, however, we found that there is a unique kink in the middle of DNA similar to an A-form conformation. Upon activation, CueR imposes a torsional stress on the DNA that stabilizes the A-form-like kink conformation. This work initiated my nucleosome work where I am trying to create a coarse-grained model to study nucleosome formation. The initial results suggest that GC-rich DNA segments are more flexible than AT-rich DNA segments. These results are in line with the previous reports where Schatz and co-workers have found that water hydration at minor groove happens in AT-rich DNA segments. Furthermore, we found out that arginine side chains in histone octamers interact with the free carbonyl groups of AT base pairs in nucleosomal DNA via water bridges. There are 14 DNA-protein interaction sites in nucleosomes, and we hypothesize that the nucleosome formation is enhanced by the formation of these water bridges. These results will be used in the parameterization of coarse-grained model to study nucleosome formation.

If you would like to attend this Seminar, please use the "Contact us" link below to arrange site access. 

Event Time & Dates

Starts01:00 pm - 25/02/2015
Ends02:00 pm - 25/02/2015

Event Details

Contact Dr Pinar Pir
LocationThe Brian Heap Seminar Room
SpeakerDr Ilyas Yildirim
Speaker AffiliationUniversity of Cambridge
Speaker Linkhttps://ilyasyildirim.wordpress.com/

Posted

5 February, 2015