Enzymes histone modification

Holbert MA, Marmorstein R (2005) Structure and activity of enzymes that remove histone modifications. Curr Opin Struct Biol 15 673-680... 

Knowledge of the detailed mechanism underlying circadian rhythms continues to be refined as new experiments reveal novel facets of the oscillatory machinery. Thus, a link has recently been established between chromatin structure and the circadian oscillatory mechanism. The CLOCK protein indeed functions as a histone acetyltransferase [116]. This enzyme activity is required for oscillations so that histone modification and the associated chromatin remodeling are implicated in the origin of circadian rhythmicity. 

Mass spectrometry provides a more direct and precise technique to study histone modifications. As with the other methods discussed above, mass spectrometry also has several pitfalls that should be taken into account when analyzing histone modifications. First of all histones and especially the core histones H3 and H4 are rich in lysine residues. Consequently, trypsin as an enzyme that is routinely used for the identification of proteins via peptide mass fingerprints cannot be used for regular in gel digestion of histones. Other enzymes that have a different specificity (such as Asp-N or Arg-C) are more frequently used in the analysis of histones [25]. A drawback... 

It is currently believed that double-stranded break (DSB) repair enzymes may act as baits to attract invading T-DNA molecules to the sites of integration. This DSB repair machinery may be transported via histone modifications as part of a general process of intranuclear protein traffic that also allows transcriptional factors to reach their target promoters (Lacroix et al., 2006b). 

The DNMTs at least partially account for the interaction of DNA methylation with histone modification as these enzymes are able to directly recruit histone deacetylases (HDACs) and this is achieved by binding methylated C ( etQ binding proteins such as MeCP2, MBD1, MBD2, and MBD3 (detailed reviews in Refs. 24 and 25). 

Histone modifications, such as phosphorylation, acetylation, and methylation, regulate gene expression. " Histone lysine methylation was considered a static modification, until relatively recently, when histone demethylases were discovered." One such enzyme is ESDI, which belongs to the amine oxidase superfamily. ESDI catalyzes the demethylation of mono- and disubstituted Eys 4 of histone H3" in a reductive halfreaction very similar to those catalyzed by DAAO and MAO by oxidizing the amino group of the methylated lysine to the corresponding imino product, which hydrolyzes nonenzymatically to formaldehyde (Equation (2)). 

In general, transcriptional activators can bind and recruit HATs while transcriptional repressors and corepressors interact with HDACs. The unwinding of DNA offhistones by lysine acetylation is conceptually helpful for understanding the action of HATs and HDACs. It is, nevertheless, a simplistic and incomplete explanation for the way in which these enzymes control gene expression. For example, in some cases [4] inhibition of HDACs can lead to a counterintuitive decrease in gene expression. It is likely that the overall pattern of histone modification (of which acetylation is but one example) represents... 

Yoshihara K, Hashida T, Tanaka Y, Matsunami N, Yamagushi A, Kamiya T (1981) Mode of enzyme-bound poly(ADP-ribose) synthesis and histone modification by reconstituted poly-(ADP-ribose) polymerase-DNA-cellulose complex. J Biol Chem 256 3471-3478... 

Chemical Biology of Histone Modifications Table 5.4 Histone methyltransferase enzymes. 

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