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

tel-00413908, version 1 - 7 Sep 2009
I.5.1.2 ATP binding and hydrolysis
As the name implies, remodelers require ATP hydrolysis to carry out structural alterations in
the nucleosomes. For SWI/SNF remodelers, the ATPase activity is stimulated by single-
stranded, double-stranded, or nucleosomal DNA to the same extent (Côté et al., 1994; Cairns
et al., 1996). In contrast, ISWI group of remodelers exhibit maximal ATPase activity with
nucleosomes while presence of free DNA does not stimulate it (Tsukiyama and Wu, 1995;
Georgel et al., 1997). Moreover, ISWI group of remodelers require the N-terminal tail of H4
for full stimulation of their ATPase activity (Clapier et al., 2001; Corona et al., 2002).
However, removal of H4 tail does not diminish binding of ISWI, suggesting that this tail may
play a role in coupling ATP hydrolysis to conformational changes in the nucleosomes. Under
optimal conditions, SWI/SNF remodelers exhibit 2-3 fold higher turnover for ATP as
compared to ISWI remodelers. For, both SWI/SNF and ISWI group of remodelers, the
stimulation of ATPase activity by DNA shows a length dependence over a limited range of
20-70 bases (Saha et al., 2002; Whitehouse et al., 2003). As mentioned before, although the
remodelers belong to SF2 superfamily of helicases they lack double strand displacement
activity (Côté et al., 1994). SWI/SNF action does not lead to enhanced sensitivity of
nucleosomal DNA to potassium permanganate, indicating a lack of transient duplex
unwinding (Côté et al., 1998). However, the helicase regions present in the ATPase subunit
are essential for SWI/SNF activity as mutations in these regions diminish the ATPase activity
(Côté et al., 1994). Furthermore, the ATPase domains in isolation exhibit limited activity
(Corona et al., 1999; Phelan et al., 1999). In summary, different remodelers exhibit both
similarity and differences in terms of substrate preference for ATPase activity.
I.5.1.3 Nucleosome disruption activities
ATP dependent remodeling on nucleosomes results in a variety of changes in the nucleosome
structure. A common feature of all chromatin remodelers is the ability to enhance accessibility
to nucleases or transcription factors. In the following sections, the different outcomes of
nucleosome remodeling lead to enhanced accessibility are summarized (See Figure I.23 for a
general summary of various outcomes of nucleosome remodeling)
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