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Bioscience Initiative - Universiteit Leiden

Bioscience Initiative

Bioscience Initiative
Leiden University

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The role of nucleosome positioning in genome function and evolution

Van Leeuwenhoek Lecture on BioScience.

Thursday June 29 2017 at 16.00hrs.
Gorlaeus, LUMY 04.28
Alain Arneodo

Alain Arneodo got his thesis in Elementary Particle Physics at the University of Nice in 1976.Then he switched his scientific interest to dynamical system theory which led him to move to the Centre de Recherche Paul Pascal (CNRS) in Bordeaux, to collaborate with an experimental group working on chemical chaos. In 2002 he moved with his group to Ecole Normale Superieure of Lyon to build a new laboratory at the physics-biology interface. In 2016 he returned to Bordeaux where he works at LOMA (Laboratoire Ondes et Matière d'Aquitaine).

Alain Arneodo's scientific contribution encompasses many fields of modern physics including statistical mechanics, dynamical systems theory, chemical chaos, pattern formation in reaction-diffusion systems, fylly-developed turbulence, the mathematics of fractals and multifractals, fractal growth phenomena, signal and image processing, wavelet transform analysis and its applications in physics, geophysics, astrophysics, chemistry, biology and finance. During the past 15 years, Alain Arneodo has published several significant papers concerning the analysis of genomic seqences using space-scale wavelet techniques. His current scientific projects consists in bridging the gap between DNA sequence analysis and the study of structure and dynamics of biological macromolecules (DNA, proteins and their interactions).

Alain Arneodo is Director of Research at the CNRS (Centre National de la Recherche Scientifique en France). He is a fellow of the Société Francaise de Physique and of the Société Européenne de Physique. He received (Brussels, 2005) the "Prix de l'Academie Royale des Sciences, Lettres et Beaux-Arts de Belgique".

We use a physical model of nucleosome formation based on sequence dependent DNA bending properties to investigate the role of nucleosome positioning in genome function and evolution. We show the existence in most eukaryotic organisms of nucleosome-inhibiting energy barriers (NIEBs) that condition the statistical positioning of neighbouring nucleosomes. In S. cerevisiae, most of the nucleosome depleted regions (NDRs) observed in vivo at transcription start sites (TSS) and active DNA replication origins indeed correspond to NIEBs, up to some shape remodeling and phasing. If similar sequence-driven NDR regulation of transcription and replication initiation is likely to operate in different yeast species and probably C. elegans, the situation is quite different in mammals where a high nucleosome affinity (high local GC content) is programmed at regulatory sequences to intrinsically restrict access to regulatory information that will mostly be used in vivo in an epigenetically-controlled cell-type dependent manner. In human, 1,6 millions of NIEBs and flanking nucleosome ordering ae observed both in vitro and in vivo as covering about 35% of the genome. Likely encodes in the local GC content, these 1 kb-size regions of intrinsic nucleosome ocupancy are equally found in GC-rich and GC-poor isochores, in early and late replicating regions, in intergenic and genic regions but not at gene promoters and replication initiation loci. The comparison of interspecies and intraspecies rates of divergence confirms the existence of some selection pressure to maintain both an optimal GC content depletion in NDRs relative to the formal bulk GC content. We propose that these widely distributed chromatin patterns have been selected in human, and more generallty in mammals and other higher eukaryotes, to impair the condensation of the nucleosomal array into the 30nm chromatin fiber, so as to facilitate the epigenetic regulation of nuclear functions in a multi-scale cell-type specific fashion.

Please keep ther following dates free in your diary (all Thursdays at 16 h):

September 28 2017, Paul Hooykaas (UL)

October 26 2017, Justin Nodwell (Toronto)

November 30 2017, Donald Canfield (Odense)