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

tel-00413908, version 1 - 7 Sep 2009
Some of the ISWI family of remodelers tend to move the nucleosomes to central position on a
DNA template, while others seem to randomise nucleosome positioning (Fan et al., 2003;
Hamiche et al., 2001). Role of additional subunits have been implicated in such observed
behaviour of these remodelers (Yang et al., 2006). On the other hand SWI/SNF group of
remodelers shift nucleosomes to the end of the DNA template, away from the
thermodynamically preferred position (Flaus and Owen-Hughes, 2003). An interesting feature
of SWI/SNF induced nucleosome shifting is that the nucleosomes could be moved ~50 bp
beyond the end of the DNA (Kassabov et al., 2003). The ability of SWI/SNF to move the
nucleosomes off the ends of DNA could explain some previously reported outcomes of
SWI/SNF mediated remodeling. SWI/SNF has been shown to generate di-nucleosome like
species or transfer of histone octamer by remodeling mononucleosomes (Lorch et al., 1998,
2001; Schnitzler et al., 1998; Phelan et al., 2000). One can imagine that as the nucleosome is
pushed off the DNA fragment, it can be transferred to another DNA or to other slided
nucleosome. It must be noted that, however, the abovementioned two outcomes are not the
major products of remodeling, at least in vitro, and could be generated in the specific reaction
conditions used by the authors.
There is some evidence that nucleosome sliding happens in vivo. It has been shown that on
the interferon beta promoter, which is activated by infection of cells with RNA viruses, the
assembly of a complete enhancesome and preinitiation complex occurs lacking only in TBP
on the promoter. However, the interaction of SWI/SNF to the promoter is essential for
initiation of transcription. Examination of nucleosome positioning before and after
transcriptional activation revealed that a nucleosome obscuring TATA sequence was moved
to position about 35 bp downstream, thereby permitting TBP to bind and allowing
transcription to occur (Agalioti et al., 2000; Lomvardas and Thanos, 2002). Similarly, in yeast
Isw2 has been shown to mobilize nucleosomes. The authors used a galactose inducible allele
of ISW2 to study changes in chromatin structure of promoters of test genes. The data
suggested that changes were unidirectional and only involved a few nucleosomes (Fazzio and
Tsukiyama, 2003).
In summary, ATP dependent chromatin remodelers are able to mobilize nucleosomes in vitro
as well as in vivo. The obvious consequence of nucleosome sliding would be to expose or
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