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

tel-00413908, version 1 - 7 Sep 2009
nucleosome disruption activity (Tsukiyama et al., 1999; Gelbart et al., 2001). Thus, ISW2 can
be considered as CHRAC homolog of yeast.
Likewise, several ISWI-containing complexes such as RSF, hACF, WCRF and hCHRAC
(reviewed by Längst and Becker, 2001) have been identified in higher eukaryotes including
Xenopus laevis (Guschin et al., 2000), mouse (Lazzaro and Picketts, 2001) and human
(Strohner et al., 2001; Aalfs et al., 2001). These complexes contain homologous counterparts
of Drosophila proteins for example hCHRAC contains subunits that are conserved in
Drosophila ISWI complexes: hACF1, the human homologue of Drosophila Acf1, a subunit of
ACF, and the human counterparts of two novel histone-fold proteins hCHRAC 15 and 17 that
are part of Drosophila CHRAC. Similar to yeast, two ISWI genes have been identified in
humans namely hSNF2L and hSNF2H (Okabe et al, 1992., Aihara et al., 1998). Both the
genes encode for proteins with about 70% homology to dISWI. hSNF2H is a member of at
least two complexes: RSF (Remodeling and Spacing Factor) and hACF/WCRF (Williams
syndrome transcription related Chromatin Remodeling Factor). RSF consists of hSNF2H and
a 325kDa polypeptide and it exhibits promoter-specific remodeling and nucleosome spacing
activities (LeRoy et al, 1998). On the other hand, in hACF complex hSNF2H is found to be
associated with WCRF180/BAZ1A (Bochar et al., 2000). WCRF180 shares all conserved
motifs of Acf1 thus hACF exhibits chromatin remodeling activities similar to Drosophila
ACF complex. Any complex containing hSNF2L has not yet been identified.
Besides the conserved Swi2/Snf2 ATPase domain, several structural domains have been
identified in the catalytic and accessory subunits of ISWI complexes such as SANT, SLIDE
(SANT-like ISWI domain), HAND and AID (Acf1 Interaction Domain) domains (Figure I.18,
Grüne et al., 2003). The SANT and SLIDE domains are connected by highly conserved
spacer helix. SLIDE domain mediates binding of the complex to DNA. However, deletion of
either SANT or SLIDE domains do not affect binding of the complex to nucleosomes but
deletion of SLIDE largely abolished its ATPase activity. Further, deletion of both domains
adversely affected nucleosome binding activity of the complex. Acf1 contains WAC (WSTF,
Acf1, Cbp146p), WAKZ (WSTF Acf1, KIAA0314, ZK783.4), DDT (DNA binding
homeobox and Different Transcription factors), BAZ, two PHD fingers and a bromodomain
(Ito et al., 1999). Isw1p and Isw2p of yeast share the same domain organization as that of
dISWI except that AID domain is absent in yeast counterpart. Ioc3 of ISW1a complex has no
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