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Volume 10, Issue 8 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X Structural Biology 2017
September 18- 20, 2017
Page 34
conferenceseries.com
9th International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
John van Noort, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100
The structure of chromatin; single-molecule experiments on model fibers and real genes
The folding of chromatin defines access to our genes and therefore plays a pivotal role in transcription regulation. However,
the structure of chromatin fibers is poorly defined and heavily debated. We used single-molecule techniques to probe
and manipulate the dynamics of nucleosomes in individual chromatin fibers. These novel methods were initially applied
to synthetic, highly homogeneous nucleosomal arrays and yielded unprecedented insight in the structure and dynamics of
chromatin. With single pair Forster Resonance Energy Transfer, we showed that the nucleosome is very dynamic, unwrapping
half of its DNA four times per second. Using single molecule force spectroscopy, it was possible to measure the kinetics of this
unfolding, both in single nucleosomes and in well-defined arrays of nucleosomes that fold into a 30 nm fiber. Analysis of the
unfolding pattern reveals a linker length dependence of the higher order folding. The linker length in vivo however varies,
and to obtain insight the positioning of nucleosomes we developed a simple statistical physics model that captures sequence
dependent positioning effects for both reconstitutions on synthetic DNA and chromatin in vivo. We recently developed a
method to purify specific chromatin fragments from yeast without crosslinking the fiber while maintaining the complexity that
provides functionality to our epi-genome. I will show the first single-molecule force spectroscopy results on intact, native fibers
which uniquely probe chromatin structure, composition and variations in it at the single-molecule level.
Biography
Chromatin is the ubiquitous protein-DNA complex that forms the structural basis of DNA condensation in all eukaryotic organisms. Packaging and depackaging of chro-
matin, called chromatin remodeling, plays a central role in all cellular processes that involve chromosomes such as transcription, replication, recombination and repair.
Detailed knowledge of the principles and mechanisms underlying this control of DNA condensation is thus vital for understanding many diseases, including neurological
disorders and cancer. The physical mechanisms governing these processes however, are still largely unknown. I am interested in developing and using modern biophysical
techniques to unravel the physics behind DNA condensation and its role in transcription regulation.
John van Noort
Leiden University, The Netherlands