H3K9 does double duty. It can turn genes on by getting acetylated, but can silence them just as easily when methylated. H3K9ac is a particularly important acetylation: it is highly correlated with active promoters. H3K9ac also has a high co-occurrence with H3K14ac and H3K4me3 which together are these three marks are the hallmark of active gene promoters (Karmodiya et al., 2012).
Histone H3K9 Variants
Mono, di, and tri H3K9 methylations each have very distinct distributions. H3K9me1 is enriched at the transcriptional start site of active genes (Barski et al., 2007). The same study found that H3K9me2/3 were both found more often at silenced genes. However it is important to note that for all these methylations that the correlations were modest, with many highly active genes showing strong H3K9me2/3 enrichment at their promoters.
Histone H3K9 Function
H3K9 methylation is the mark of heterochromatin. Heterochromatin is the condensed, transcriptionally inactive state of chromatin. It can be facultative or constitutive. H3K9me3 binds heterochromatin protein 1 (HP1) to constitutive heterochromatin (Lehnertz et al., 2003). HP1 is responsible for transcriptional repression and the actual formation and maintenance of heterochromatin. HP1 also recruits DNA methyltransferase 3b, providing one of the best examples of the interplay between histone methylation and DNA methylation.
H3K9me2 is a characteristic mark of the inactivated X chromosome (Xi) (Rougeulle et al., 2004). A recent paper describes how a new protein has been implicated in H3K9me2 mediated X inactivation (Escamilla-Del-Arenal et al., 2013). The protein Cdyl was shown to not only bind H3K9me2 and H3K27me3 on Xi, but also the H3K9 histone methyltransferase G9a. The authors propose that early H3K9me2 is propagated by recruitment of Cdyl and thus G9a which then triggers further H3K9me2 and propagates it though cell division.
Histone H3K9 Additional Reading:
Shinkai, Y., and Tachibana, M. (2011). H3K9 methyltransferase G9a and the related molecule GLP. Genes Dev. 25, 781-788.
This review focuses on H3K9 specific methyltransferases, specifically G9a, and their role in regulation of gene expression. It also highlights some interesting data on the roles of G9a in various processes.
Hashimoto, H., Vertino, P.M., and Cheng, X. (2010). Molecular coupling of DNA methylation and histone methylation. Epigenomics 2, 657-669.
This review highlights some of the known protein domains that link DNA methylation and histone methylation. Several proteins are listed, and a great deal of primary data is given for each.
- Barski, A., Cuddapah, S., Cui, K., Roh, T.Y., Schones, D.E., Wang, Z., Wei, G., Chepelev, I., and Zhao, K. (2007). High-resolution profiling of histone methylations in the human genome. Cell 129, 823-837.
- Escamilla-Del-Arenal, M., da Rocha, S.T., Spruijt, C.G., Masui, O., Renaud, O., Smits, A.H., Margueron, R., Vermeulen, M., and Heard, E. (2013). Cdyl, a new partner of the inactive X chromosome and potential reader of H3K27me3 and H3K9me2. Mol. Cell. Biol. 33, 5005-5020.
- Lehnertz, B., Ueda, Y., Derijck, A.A., Braunschweig, U., Perez-Burgos, L., Kubicek, S., Chen, T., Li, E., Jenuwein, T., and Peters, A.H. (2003). Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin. Curr. Biol. 13, 1192-1200.
- Rougeulle, C., Chaumeil, J., Sarma, K., Allis, C.D., Reinberg, D., Avner, P., and Heard, E. (2004). Differential histone H3 Lys-9 and Lys-27 methylation profiles on the X chromosome. Mol. Cell. Biol. 24, 5475-5484.
- Karmodiya, K., Krebs, A.R., Oulad-Abdelghani M., Kimura, H., Tora, L. (2012). H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells. BMC Genomics. 13:424.