H3K9 methyltransferase G9a and the related molecule GLP

Abstract

The discovery of Suv39h1, the first SET domain-containing histone lysine methyltransferase (HKMT), was reported in 2000. Since then, research on histone methylation has progressed rapidly. Among the identified HKMTs in mammals, G9a and GLP are the primary enzymes for mono- and dimethylation at Lys 9 of histone H3 (H3K9me1 and H3K9me2), and exist predominantly as a G9a-GLP heteromeric complex that appears to be a functional H3K9 methyltransferase in vivo. Recently, many important studies have reported that G9a and GLP play critical roles in various biological processes. The physiological relevance of G9a/GLP-mediated epigenetic gene regulation is discussed.

Figure 1.

Domain organization of the core G9a complex components: G9a, GLP, and Wiz. Amino acid sequences of mouse (m) G9a-L (9QZ148), mGLP (A2AIS4), and mWiz (O88286-2). (K) Potential methylation sites by G9a or GLP (K167 and K239 in G9a-L, K154 and K206 in GLP, and K467 in Wiz) (Sampath et al. 2007; Rathert et al. 2008); (E) Glu-rich region; (E/D) Glu/Asp-rich region; (Cys) Cys-rich region; (Pre) pre-SET domain; (SET) SET domain; (Post) post-SET domain; (Z) zinc finger motif; (CID) CtBP-interacting region (Ueda et al. 2006).

Figure 2.

Multiple biological roles of G9a/GLP. Multiple biological roles of G9a/GLP are proposed, based mainly on the results of studies using G9a or GLP knockout mice.