Histone methyltransferase

The attachment of methyl groups occurs predominantly at specific lysine or arginine residues on histones H3 and H4.

[2][3][4] In both types of histone methyltransferases, S-Adenosyl methionine (SAM) serves as a cofactor and methyl donor group.

The SET domain itself contains a catalytic core rich in β-strands that, in turn, make up several regions of β-sheets.

[1] In order for the reaction to proceed, S-Adenosyl methionine (SAM) and the lysine residue of the substrate histone tail must first be bound and properly oriented in the catalytic pocket of the SET domain.

[1] A possible homolog of Dot1 was found in archaea which shows the ability to methylate archaeal histone-like protein in recent studies.

[15] The differences in methylation patterns of PRMTs arise from restrictions in the arginine binding pocket.

Abnormal expression or activity of methylation-regulating enzymes has been noted in some types of human cancers, suggesting associations between histone methylation and malignant transformation of cells or formation of tumors.

It is now generally accepted that in addition to genetic aberrations, cancer can be initiated by epigenetic changes in which gene expression is altered without genomic abnormalities.

[18] There is not yet compelling evidence that suggests cancers develop purely by abnormalities in histone methylation or its signaling pathways, however they may be a contributing factor.

[18][19][20] The methylation of histone lysine has an important role in choosing the pathway for repairing DNA double-strand breaks.

Additionally, many questions still remain about the function and regulation of histone methyltransferases in malignant transformation of cells, carcinogenesis of the tissue, and tumorigenesis.