Abstract :
[en] 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.
Scopus citations®
without self-citations
0
