Histones histone methylases

Histone-lysine methyltransferases are chromatin-bound enzymes that catalyses the addition of methyl groups onto lysine or arginine residues of chromatin-bound H3 and H4 [151]. The methyl group is transferred enzymatically to the histone with S-adenosyl methionine as the methyl donor. Histone methylases have been isolated from HeLa S-3 cells [182], chick embryo nuclei [183], and rat brain chromatin [184]. The histone methyltransferases methylated H3 and H4 in nucleosomes [184]. Histone-lysine methyltransferase is a chromatin-bound enzyme [129,151]. Initial characterization of the Tetrahymena macronuclear H3 methyltransferase suggests that the enzyme has a molecular mass of 400 kDa. The enzyme preferred free histones rather than nucleosomes as substrate [138]. More recent studies have now... 

Fig. 8. Proposed models that link histone methylation to DNA methylation (for details see Section 5.2). Methylated cytosines attract histone methyltransferases that contain a methyl-binding domain or a methyl-CpG binding protein (MeCP2) that recruits histone methylase activities these introduce methyl groups into the histone tails. The binding of chromodomain HPl proteins to H3 tails methylated at lysine 9 generates a secondary layer of repressive chromatin structure, (b) In a reverse scenario, methylated histone tails attract chromodomain-binding proteins, which in turn recruit Dmnts to methylate adjacent DNA sequences.

Ng, H.-H., Robert, F., Young, R.A., and Struhl, K. (2003) Targeted recruitment of Setl histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol. Cell 11, 709-719. 

Discuss the roles of the following proteins in development receptors, transcription factors, protein kinases, histones, DNA methylases, adhesion molecules, ubiquitin. How do small RNA molecules participate in development ... 

A number of proteins such as histones, cytochrome c and certain flagellar proteins are found to contain methylated amino acids (19). Three different methylases have been characterized and all require S-adenosylmethionine (SAM) as the methyl donor (20-23). Protein methylase I (SAM-protein arginine methyl transferase) methylates the guanidine side chain of arginine residue protein methylase II (SAM-protein carboxyl methyltransferase) transfers methyl groups only to 8- and y-carboxyl groups in the peptide chain. Carboxyl groups in the a position cannot serve as acceptors. Protein methylase III (SAM-protein lysine... 

Ghosh, S. K., Paik, W. K., Kim, S. (1988). Purification and molecular identification of two protein methylases 1 from calf brain myelin basic protein- and histone-specific enzyme. J. Biol. Chem. 263, 19024-19033. 

Protein (lysine) Methyltransferase. The enzyme which methylates lysine residues of proteins was named protein methylase III by Paik and Kim (210). Its recommended trivial name is protein (lysine) methyltransferase (S-adenosyl-L-methionine protein-lysine methyltransferase EC 2.1.1.25). Protein (lysine) methyltransferase was found in all rat organs examined and was localized exclusively in the nuclei. Paik and Kim (210) solubilized the enzyme from an acetone powder of calf thymus and purified it 1.3-fold. The enzyme was difficult to work with in the solubilized state, since its activity was lost on overnight storage at either — 10° or 3°C. The enzyme was most effective in methylating histones, especially arginine-rich histone. Denaturation of histone by heating at 100°C for 30 min had no effect on the rate at which protein-lysine) methyltransferase methylated it. Poly lysine and protamine were methylated at slower rates, but horse heart cytochrome c did not serve as substrate. Km for S-adenosyl-L-methionine was 3.0 X 10"6M. 

In addition to elevated AdoMet levels, trypanosomes treated with DFMO in vivo experience a six-fold increase in the activity of protein methylase II but not I or III (55). Protein methylase II specifically methylates carboxyl groups of aspartate and glutamate residues. In mammalian cells, histone methylation may be involved in the condensation of euchromatin to heterochromatin prior to mitosis (56-58), and may therefore have a role in gene expression. Aspartate- and glutamate-rich histones have also been characterized from both T. b. brucei and Crithidia fasciculata making these likely substrates for protein methylase II activity (59,60). 

Using histones as substrate, Baxter and Byvoet (25) observed that partially purified rat liver protein methylase I could utilize both S-adenosyl-L-methionine and S-adenosyl-L-ethionine as alkyl donor with cosqparable efficiency. On the other hand, Cory et al. 

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