Description
Epigenetic activation or inactivation of genes plays a critical role in many important human diseases, especially in cancer. A major mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA caused by DNA methyltransferases. Histone methyltransferases (HMTs) control or regulate DNA methylation through chromatin-dependent transcription repression or activation. HMTs transfer 1-3 methyl groups from S-adenosyl-Lmethionine to the lysine and arginine residues of histone proteins. SET1, SET7/9, Ash1, ALL-1, MLL, ALR, Trx, and SMYD3 are histone methyltransferases that catalyze methylation of histone H3 at lysine 4 (H3-K4) in mammalian cells. H3- K4 tri-methylation has been viewed as a signature mark of highly transcribed genes, which is placed exclusively in the 5"- region downstream of the promoter. Increased H3-K4 tri-methylation is also found to be involved in some pathological processes such as cancer progression. The H3-K4 trimethylation can be also changed by inhibition or activation of HMTs. Thus, quantitative detection of tri-methyl histone H3-K4 would provide useful information for better understanding epigenetic regulation of gene activation, and for developing HMT-targeted drugs