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

tel-00413908, version 1 - 7 Sep 2009
in eukaryotic evolution and is present in the mammals, birds (H2A.F), the Drosophila (H
2Av), C. elegans, sea urchins (H2AZ/F), various protozoans like Tetrahymena (H2Ahv1) and
yeast (Htz1) (Raisner et al., 2005). Likewise, H2A.X is also present in all eukaryotes whereas
the variant macroH2A exists only in vertebrates and H2A.Bbd is found exclusively in
mammals (Malik and Henikoff, 2003; Eirin-Lopez et al., 2008).
Figure I.10 Phylogenetic tree of H2A variants. Adapted from Gonzalez-Romero et al., 2008.
I.4.1.2.1 H2A.Z The variant H2A.Z shares only around 60% homology with the canonical
H2A and 90% homology between species. The resolution of crystal structure of nucleosome
containing H2A.Z by Suto et al., (2000) revealed that DNA trajectory is not distorted by
replacement with this variant however, protein-protein interactions are affected. Differences
in affinity between H2A-H2B dimer and the core tetramer were observed. Three hydrogen
bonds were found to be lost, thus destabilizing the interaction between H3 and H2A.Z.
However, the dimer H2A.Z-H2B forms a strong acidic patch and a divalent cation binding
site on the surface through which it could bind more strongly to H4 tail or other interacting
non-histone proteins (Suto et al., 2000). Also, it could support the formation of 30 nm fiber.
Several studies reporting contradictory physical properties of H2A.Z variant have been
published; these differences in observations are might be due to the difference in techniques
used in the studies. For example, certain measurements conclude that the nucleosome
containing H2A.Z would be less stable (Abbott et al., 2001) while others found it to be highly
stable (Fan et al., 2002; Park et al., 2004; Jin and Felsenfeld, 2007).
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