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

tel-00413908, version 1 - 7 Sep 2009
H2A.Z has been observed to be located at yeast promoters and display a redundant role with
ATP-dependent nucleosome remodeling complexes (Santisteban et al., 2000) and found to
interact directly with transcriptional machinery during gene expression (Adam et al., 2001).
Flaus et al., (2004) observed that H2A.Z nucleosomes can slide thermodynamically more
quickly than conventional nucleosomes at around 30°C. This important observation
strengthened their property similar to remodeling complexes such as SWI/SNF. Various
groups determined genome wide localization of H2A.Z nucleosomes (Guillemette et al.,
2005; Li et al., 2005a; Raisner et al., 2005; Zhang et al., 2005; Millar et al., 2006; Barski et
al., 2007). All these works point towards localization of a large fraction of H2A.Z
nucleosomes on promoter regions. However, the correlation between the presence of H2A.Z
on the promoter and activity of the gene is not known for all and is still discussed. Recently,
Baski et al., (2007) carried out high-resolution analysis of H2A.Z positioning in human
genome, using SOLEXA© sequencing technique and found that, contrary to yeast, the
presence of H2A.Z on the promoter is correlated with an active transcription in humans.
These studies with high-resolution positioning of H2A.Z on the genome show that H2A.Z is
strongly enriched in the nucleosome free area (NFR) of promoters (Raisner et al., 2005;
Barski et al., 2007). This work shows that two nucleosomes containing H2A.Z flank the NFR
of the promoter, in yeast and in human (Raisner et al., 2005; Barski et al., 2007). This led to
identification of a 22 bp consensus sequence that could promote formation of NFR and
incorporation of H2A.Z in both nucleosomes flanking this area (Raisner et al., 2005). In yeast,
acetylation of histones also directs incorporation of H2A.Z in euchromatic regions (Raisner et
al., 2005; Zhang et al., 2005). Hence, H2A.Z targets specific nucleosomes within promoters
and can create promoter-specific chromatin structures, However, H2A.Z enrichment in active
chromatin may even lead to repression of gene expression (Dhillon and Kamakaka, 2000)
hence; its role in functional chromatin dynamics is enigmatic.
In vitro, the presence of H2A.Z facilitates nucleosomal fiber compaction, but inhibits
oligomerization (Fan et al., 2002). This suggests that chromatin containing H2A.Z could be
present in the heterochromatic region. In parallel, HP1α (a protein known to be related to
constitution and compaction of heterochromatin) was found to bind preferentially to
chromatins reconstituted with H2A.Z in vitro and absence of H2A.Z changes HP1α protein
localization, in vivo (Fan et al., 2004). These results indicate involvement of H2A.Z in
formation of pericentric heterochromatin.
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