Etudes sur le mécanisme de remodelage des nucléosomes par ...

tel-00413908, version 1 - 7 Sep 2009
crosslinked to the DNA, and the remodeling was assessed by sensitivity to nucleases.
Interestingly, hSWI/SNF could still increase the sensitivity towards DNaseI even in the
absence of nucleosome movement. Using a photo affinity labelling and crosslinking
approach Kassabov et al., (2003) have shown that SWI/SNF moves the nucleosomes in
increments of ~50 bp while for ISWI the step size was ~10 bp. These were interpreted as the
size of the loop or the bulge created by these remodelers. Using this information about the
step size authors have tried to explain the observed differences in nucleosome disruption
properties of these two remodelers. It must be noted that, however, that new histone DNA
crosslinks generated due to remodeling could represent final products of the remodeling rather
than reaction intermediates. Another support towards formation of bulge by remodelers come
from the fact that remodelers are ATP dependent DNA translocases and are able to pump
DNA inside the nucleosome (Saha et al., 2005; Zofall et al., 2006).
Figure I.24 Proposed models of nucleosome sliding by ATP dependent remodelers.
(A) Schematic drawing of the SHL locations that form DNA– histone interaction clusters. (B) and (C)
The essential features of the nucleosome remodeling models. Adapted from Langst and Becker, 2004.
Another model for RSC mediated nucleosome movement was proposed by Saha et at., (2005).
Under this model DNA is moved in form of a 1 bp wave from the internal translocation site to
the end of the nucleosome. However, if it was the case nucleotide gaps anywhere within this
region would interfere with nucleosome mobilization. It was seen that nucleotide gaps created
only within or near the translocation site interfere with nucleosome mobilization questioning
the validity of this model. Importantly, till date, no direct demonstration of a bulge formation
on the nucleosome surface has been done and evidences provided are only indicative.
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