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

tel-00413908, version 1 - 7 Sep 2009
et al., 2002; Ng et al., 2003; Santos-Rosa, et al., 2002) while di- and tri-methylation of lysine
9 or 23 of H3 leads to gene silencing (Bannister et al., 2001; Cao et al., 2002; Czermin et al.,
2002; Lachner et al., 2001). Heterochromatic regions are especially enriched in methylated
histones. HP1 binds to di- and tri-methylated form of lysine 9 of H3 (Bannister et al., 2001;
Lachner et al., 2001) but this binding is inhibited at the beginning of phase S due to
phosphorylation of its serine 10 residue by AuroraB kinase (Fischle et al., 2005). Another
protein polycomb, involved in silencing of homeotic genes during development, recognizes
methylation of lysine 27 of H3. These proteins bind to methylated histones through their
chromo-domain (Brehm et al., 2004).
I.4.2.3 Other histone covalent modifications
Besides acetylation and methylation, histones can undergo phosphorylation at serine residues
e.g. serine 10 and 28 of H3 (Fischle et al., 2003). Several kinases and phosphatases are
involved in regulation of histone phosphorylation such as aurora kinase and Glc7/PP1
phosphatase (Hsu et al., 2000). This modification is associated with mitotic chromosome
condensation. Besides core histones, the linker histone H1 has also been shown to undergo
phosphorylation, methylation and ADP-ribosylation (Godde and Ura, 2008; Villar-Garea and
Imhof, 2008). Like H3, methylation of lysine 26 of H1.4 supports HP1 binding whereas
phosphorylation of serine 27 blocks this (Daujat et al., 2005). HP1 binding can be blocked by
phosphorylation of H1.5 (or H1b) suggesting a simple redundancy between the five
phosphorylation sites of this histone (Hale et al., 2006). Phosphorylation of H2A variant,
H2A.X has also been well described in DNA repair (Double strand breaks) (Marzluff and
Pandey, 1988; Rogakou et al., 1998; Li et al., 2005b).
Further, histones can get ubiquitinated by addition of a 76 aa peptide to lysine residue e.g.
lysine 123 of H2B. This modification is a prerequisite for methylation of lysine 4 and 79 of
H3 (Briggs et al., 2002; Sun and Allis, 2002). Hence, there seems to be a crosstalk between
these covalent modifications and together they make a signature on the chromatin. In
addition, a variety of other histone modifications has been described, such as ADP-
ribosylation, biotinylation, glycosylation and sumoylation. Role of ADP-ribosylation has been
implied in DNA repair (D'Amours et al., 1999; Lindahl et al., 1997). Further role of histone
modifications has been implicated in cell ageing (Vaquero et al., 2003).
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