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

tel-00413908, version 1 - 7 Sep 2009
its clear evidence came with development of antibodies against specific acetylated histones
(Turner et al., 1992). Later, Brownell et al., (1996) and others identified enzymes mediating
histone acetylation modifications. Now, histone acetylation has been recognized as a dynamic
modification of histone controlled by two antagonistic reactions mediated by histone
acetyltransferases (HAT) and histone deactylases (HDAC).
HATs form multiprotein complexes that display different histone tail specificities. Bromo-
domain is present in many of these proteins through which they recognize acetylated histones
(Dhalluin et al., 1999; Jacobson et al., 2000). Moreover, these proteins can physically
associate with various transcription factors helping them to target the modified histones thus
helps in targeting transcription machinery to specific genes. Likewise, many transcription
repressors are known to be associated with HDAC’s and that complex plays role in gene
silencing (Vaquero et al., 2003). Recently, HDACs are also described to be involved in
upregulation of gene expression (Kurdistani and Grunstein, 2003; Robyr et al 2002; Wang et
al 2002). Besides gene regulation, histone acetylation plays an important role in many other
nuclear processes like DNA repair and apoptosis, VDJ recombination and dosage
compensation in Drosophila (Iizuka and Smith, 2003).
I.4.2.2 Histone methylation
Methylation of lysine or arginine by histone methyltransferases (HMTs) was supposed to be a
stable mark and was discovered more than 30 years ago but its functional significance has
been recognized only recently (Rice and Allis, 2001). Moreover several demethylating
enzymes have now been recognized such as JHDM1 (Schneider and Shilatifard, 2006). Thus
like acetylation, even methylation is a reversible posttranslational modification of histones
and is associated with transcriptional regulation of genes and epigenetic silencing via
heterochromatin assembly. This posttranslational modification has best been described for
H3 and H4 (Fischle et al., 2003; Vaquero et al., 2003).
HMTs catalyze transfer of up to three methyl groups from S-adenosyl-methionine to a single
lysine residue and PRMTs (protein arginine methyltransferases) can make mono- or
dimethylated arginines, either symmetrically or asymmetrically (Kouzarides, 2002). Both, the
site of the residue and number of methyl groups attached to it, determine the functional role of
the modification (Lachner and Jenuwein, 2002; Lachner et al., 2003). For example,
methylation of lysine 4, 36 and 79 of H3 is associated with transcriptional activation (Beisel
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