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See detailDNA in chromatin: from genome-wide sequence analysis to the modelling of replication in mammals
Arbeodo, Alain; d'Aubenton-Carafa, Y.; Audit, B. et al

in Advances in Chemical Physics (2006), 135

Understanding how chromatin is spatially and dynamically organized in the nucleus of eukaryotic cells and how this affects genome functions is one of the main challenges of cell biology. In that context ... [more ▼]

Understanding how chromatin is spatially and dynamically organized in the nucleus of eukaryotic cells and how this affects genome functions is one of the main challenges of cell biology. In that context the role of the DNA sequence itself in these condensation- decondensation processes is still debated. In this chapter, we explore large-scale nucleotide compositional fluctuations along the human genome through the optics of the wavelet transform microscope. Analysis of the GC content and of the TA and GC skews re- veals the existence of rhythms with characteristic fundamental frequencies that enlighten a remarkable cooperative organization of gene location and orientation. We describe a multi-scale methodology that allows us to predict 1012 replication origins in the 22 hu- man autosomal chromosomes. We present a model of replication with well-positioned replication origins and random termination sites that accounts for the highly relaxational nature of the oscillations observed in the skew profiles. We emphasize these putative replication initiation zones as regions where the chromatin fiber is likely to be more open so that DNA be more easily accessible. We show that, in the crowded environment of the cell nucleus, the presence of these intrinsic decondensed structural defects actually pre- disposes the fiber to spontaneously form multi-looped rosette-like structures that provide an attractive description of genome organization into replication foci that are observed in interphase mammalian nuclei as stable autonomous chromatin domains favoring com- partmentalized DNA replication and gene expression. New experimental perspectives are discussed. [less ▲]

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