Poster abstracts

Poster number 8 submitted by Yi Luo

Nucleosome Rewrapping Facilitates Transcription Factor Exchange

Yi Luo (Biophysics Graduate Program, the Ohio State University), Justin A. North (Department of Physics, the Ohio State University), Lindsey Kathmann (Department of Materials Science and Engineering, the Ohio State University), Christopher Cook (Department of Molecular Virology, Immunology and Medical Genetics, the Ohio State University), Richard Fishel (Department of Molecular Virology, Immunology and Medical Genetics, the Ohio State University), Michael G. Poirier (Department of Physics, the Ohio State University)

Abstract:
Transcription factors (TFs) play a central role in regulating the transcriptional state of gene. However, TFs are sterically occluded from their target sequences when it is wrapped around the histone octamer into a nucleosome. The combination of nucleosomal DNA unwrapping fluctuations and the high DNA sequence specificity of TFs facilitate TF to binding within nucleosomes. TFs achieve their high DNA sequence specificity by having resident times at their recognition sites that are much longer than minutes. This dramatically limits the rate at which a gene can switch between transcriptionally active and repressed states. We investigated with single-molecule Fluorescence Resonance Energy Transfer measurements the influence of nucleosomal DNA wrapping fluctuations on TF binding and release from its target sequence within a nucleosome. As expected, we find that nucleosomes inhibit the binding rate of a TF to its target sequence within a nucleosome. In contrast,we observe that the rate of TF dissociation from a nucleosome is increase by over a 100-fold as compared to dissociation from duplex DNA. This result suggests that the nucleosome promotes TF dissociation to facilitate the exchange of TFs at their target sequences and enable rapid regulation of gene expression.

References:
[1]. Li G, Widom J (2004) Nucleosomes facilitate their own invasion. Nat StructMol Biol 11:763–769.
[2]. Thastrom A, Lowary PT, Widom J (2004) Measurement of histone-DNA interaction free energy in nucleosomes. Methods 33:33–44.
[3]. Davey CA, Sargent DF, Luger K, Maeder AW, Richmond TJ. Solvent mediated interactions in the structure of the nucleosomecore particle at 1.9 a resolution. J.Mol.Biol. 319:1097.

Keywords: Nucleosome, Transcription Factors, Single-Molecule