Substrate and product specificities of SET domain methyltransferases.

Abstract

SET domain lysine methyltransferases (KMTs) catalyze the site- and state-specific methylation of lysine residues in histone and non-histone substrates. These modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation and DNA damage response, and have been implicated in the epigenetic regulation of cell identity and fate. The substrate and product specificities of SET domain KMTs are pivotal to eliciting these effects due to the distinct functions associated with site and state-specific protein lysine methylation. Here, we review advances in understanding the molecular basis of these specificities gained through structural and biochemical studies of the human methyltransferases Mixed Lineage Leukemia 1 (MLL1, also known as KMT2A) and SET7/9 (KMT7). We conclude by exploring the broader implications of these findings on the biological functions of protein lysine methylation by SET domain KMTs.

• Authors: Paul A Del Rizzo, Raymond C Trievel
• Journal: Epigenetics (Epigenetics) Vol. 6 Issue 9 Pg. 1059-67 (Sep 01 2011) ISSN: 1559-2308 [Electronic] United States
• PMID: 21847010 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Histones
• KMT2A protein, human
• NF-kappa B
• Myeloid-Lymphoid Leukemia Protein
• Histone-Lysine N-Methyltransferase
• SETD7 protein, human
• Lysine

Topics

• Catalytic Domain
• Enzyme Activation
• Histone-Lysine N-Methyltransferase (chemistry)
• Histones (chemistry)
• Humans
• Lysine (chemistry)
• Methylation
• Myeloid-Lymphoid Leukemia Protein (chemistry)
• NF-kappa B (chemistry)
• Protein Interaction Mapping
• Protein Structure, Tertiary
• Structure-Activity Relationship
• Substrate Specificity