SET for life: biochemical activities and biological functions of SET domain-containing proteins

Trends Biochem Sci. 2013 Dec;38(12):621-39. doi: 10.1016/j.tibs.2013.09.004. Epub 2013 Oct 20.


SET domain-containing proteins belong to a group of enzymes named after a common domain that utilizes the cofactor S-adenosyl-L-methionine (SAM) to achieve methylation of its substrates. Many SET domain-containing proteins have been shown to display catalytic activity towards particular lysine residues on histones, but emerging evidence also indicates that various non-histone proteins are specifically targeted by this clade of enzymes. Here, we summarize the most recent findings on the biological functions of the major families of SET domain-containing proteins catalyzing the methylation of histones 3 on lysines 4, 9, 27, and 36 (H3K4, H3K9, H3K27, and H3K36) and histone 4 on lysine 20 (H4K20) as well as candidates that have been reported to regulate non-histone substrates.

Keywords: SET domain-containing proteins; histone lysine methylation; non-histone substrates.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • DNA-Binding Proteins
  • Histone Chaperones / metabolism
  • Histone Chaperones / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • Histone Chaperones
  • SET protein, human
  • Transcription Factors