Lysine, methylation

Histone methylation is a common posttranslational modification fond in histones. Histone methylations have been identified on lysine and arginine residues. In case of lysines S-adenosyl-methionine (SAM) dependent methyl transferases catalyze the transfer of one, two or three methyl groups. Lysine methylation is reversible and lysine specific demethylases have been... 

Agarwal et used glycerol in combination with PEO, lysine methyl ester dusocyanate... 

ENZYME MECHANISM AND CATALYSIS OF HISTONE LYSINE METHYLATION [49,50]... 

In addition to histone deacetylation, histone lysine methylation can also lead to gene silencing which is not blocked by the HDAC inhibitors [6, 51], Several lines of evidence have suggested a connection between cancer and histone lysine methyltrans-ferases (HKMTs) [52], HKMTs catalyze the transfer of methyl group(s) from the cofactor. S -adenosyI-methionine (AdoMet) to some specific lysine residues in the N-terminal histone tails [53, 54], With one exception of Dotl [55], all known HKMTs contain the SET domain which represents a novel structural fold [53, 56], Among SET-domain HKMTs, SET7/9 is one of the best characterized experimentally. It is a... 

Hu P, Zhang Y (2006) Catalytic mechanism and product specificity of the histone lysine methyl-transferase set7/9 An ab initio QM/MM-FE study with multiple initial structures. J Am Chem Soc... 

Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6 838-849... 

Kwon T, Chang JH, Kwak E, Lee CW, Joachimiak A, Kim YC, Lee JW, Cho Y (2003) Mechanism of histone lysine methyl transfer revealed by the structure of set7/9-adomet. EMBO J., 22 292-303... 

Lysine methylation marks Monoamine oxidase inhibitor Plant homeodomain Posttranslational modification Protein lysine methyl transferase... 

Figure 1 Covalent modifications of DNA and histones play a fundamental role in the regulation of differentiation and development. The writers, readers, and erasers of this dynamic code are potentially amenable to modulation with small molecules. Lysine methylation is a critical posttranslational modification influencing chromatin function (PMT = protein lysine methyltransferase, royal family proteins bind KMe, KDM = lysine demethylase).

LYSINE METHYLATION AS A DYNAMIC REGULATOR OF CHROMATIN FUNCTION... 

The dynamic and differential methylation of lysine residues in histone tails plays a central role in the creation of the histone code and the regulation of chromatin structure and function that the code implies [12]. For example, different lysine methylation marks (KMe) are... 

Fig. 16 Manipulation of deprotected C-glucopyranosides. Reagents and conditions (a) i. BTSFA, CH3CN, reflux ii. allyltrimethylsilane, TMSOTf, 0 °C-room temp., 12 h (b) NIS, HzO, 2 h (c) Bu4NN3, H20, 80 °C, 72 h (d) Cs2C03, Cys-NAc-OMe, MeOH-DMF 2 1 (e) hv, W-acetyl L-cvsteine methyl ester, MeOH/H20 (f) i. 03, ii. Me2S (g) W-acetyl L-lysine methyl ester, MeOH, AcOH, NaBH3CN.

Figure 16. Morphology of measured crystals of (S)-lysine-HC1 2H20 viewed along the a and c axes (a) pure (b),(c) grown in the presence of (b) (S)-lysine methyl ester, (c) (S)-norleucine.

Verschure PJ, van der Kraan I, de Leeuw W, van der Vlag J, Carpenter AE, Belmont AS, van Driel R (2005) In vivo HPl targeting causes large-scale chromatin condensation and enhanced histone lysine methylation. Mol Cell Biol 25 4552-4564... 

Markham D, Munro S, Soloway J, O Connor DP, La Thangue NB (2006) DNA-damage-responsive acetylation of pRb regulates binding to E2F-1. EMBO Rep.7(2) 192-198 Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 6(11) 838-849... 

Figure 4. Possible deposition timing of histone lysine methylation...

Kubicek S, Jenuwein T (2004) A crack in histone lysine methylation. Cell 119 903-906 Kwon HJ, Kim JH, Kim M, Lee JK, Hwang WS, Kim DY (2003) Anti-parasitic activity of depudecin on Neospora caninum via the inhibition of histone deacetylases. Vet Parasitol 112 269-276 Lau OD, Kundu TK, Soccio RE, Ait-Si-Sli S, Khail EM, Vassilev A, Wolffe AP, Nakatani Y, Roeder RG, Cole PA (2000) HATs off Selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol Cell 5 589-595... 

Methylation plays an important role in transcriptional regulation and a lesser role in signal transduction. " Histones are heavily methylated proteins. Single, double, or triple methylated lysines play an important role on histones. Lysine methylation is a more subtle transcriptional control than acetylation. Lysine methylation has come to light in another protein known as p53. p53 is a protein expressed in low levels in the cell and stabilized by posttranslational modifications including phosphorylation, acetylation, and now N-methylation. There are several C-terminal lysines on p53 that increase its stability. The addition of the methylation modifications adds complexity to p5 3 and fine-tunes its activity and ultimately suppresses tumor formation. ... 

In contrast, lysine methylation seems to be an exceptionally stable modification. Early studies showed that turnover of histone methyl groups was even slower than turnover of the histones themselves (e.g., [26,27]). No conclusive evidence has yet been found for histone demethylating enzymes, and they may not exist [28]. It may be that removal of methylated histones mostly occurs passively, through post-replication chromatin assembly and replacement of old, methylated histones with new, unmethylated ones. However, the possibility remains that local methylation patterns may be more dynamic and may involve novel mechanisms for removal of methylated tails [28]. 

Litt, M.D., Simpson, M., Gaszner, M., Allis, C.D., and Felsenfeld, G. (2001) Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus. Science 293, 2453-2455. 

Ng, H.H., Feng, Q., Wang, H., Erdjument-Bromage, H., Tempst, P., Zhang, Y., and Struhl, K. (2002) Lysine methylation within the globular domain of histone H3 by Dotl is important for telomeric silencing and Sir protein association. Genes Dev. 16, 1518-1527. 

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