Methyltransferases are enzymes that transfer a methyl group from S-adenosylmethionine (SAM) to their substrates.DNA methyltransferases modify DNA by adding a methyl group to cytosines. DNA methylation of CpG dinucleotides suppresses gene expression and is critical for transcriptional silencing during imprinting, X-inactivation and other developmental processes. DNA methylation also plays a crucial role in the development of nearly all types of cancer.
Methyltransferases can also modify proteins; histone methyltransferases methylate lysines and arginines on histone side chains. Lysines may be mono-, di-, or trimethylated and arginines may be mono-, symmetrically or asymmetrically dimethylated. Each of these different ‘flavors’ of methylation can result in different chromatin conformations and gene expression levels.
Several histone methyltransferases have been linked to diseases, in particular cancer. The lysine methyltransferase EZH2 is a prime example of this. EZH2 is a methyltransferase that is part of the Polycomb Repressive complex (PRC2). EZH2, along with EED, RbAP48, SUZ12 and AEBP2, form a 5-member complex that methylates Lysine 27 of Histone H3 (H3K27). Abnormal expression of EZH2 has been linked to breast, prostate, endometrial, and other human cancers. Several point mutations in EZH2 cause it to hypermethylate H3K27, and are strongly associated with non-Hodgkins lymphomas and leukemias. Not surprisingly, inhibition of EZH2 is a key target for anti-cancer drug discovery. To aid in discovery, BPS offers a number of EZH2 mutant enzymes.
Aside from purified enzymes, BPS offers assay kits, inhibitors/activators, and substrates. The substrates offered by BPS include purified full-length histone proteins, tetramers, octamers, nucleosomes, and a number of modified histones. This diverse portfolio provides researchers with optimal flexibility in their experiments.
1. Vire, E. et al., Nature. 2006; 439: 871-874.
2. Lyko, F. et al., J. Nat. Canc. Inst. 2005; 97(20): 1498-1506.