H3K27 is known for one thing: shutting down transcription. When H3K27 is trimethylated, it is tightly associated with inactive gene promoters. It acts in opposition to H3K4me3. Because of its dramatic and predictable effect on gene expression, H3K27me3 is a favorite of epigenetic researchers looking for inactive genes.
Most histone methylations are catalyzed by many enzymes. H3K27me3 is distinct in that it has only one known methyltransferase: EZH2 (Kuzmichev et al., 2002). EZH2 is part of the PRC2 complex which is responsible for the repression many genes involved in development and cell differentiation (Boyer et al., 2006; Bracken et al., 2006). It is thus believed that H3K27me3 is critical for the repression of developmental genes. H3K27me3 is also an important mark of the inactive X chromosome (Xi) (Rougeulle et al., 2004).
Histone H3K27 Modifications
When H3K27 is trimethylated, it is tightly associated with inactive gene promoters.The mono- and di-methylation states are less studied; however, H3K27me2 shows a similar distribution to H3K27, while H3K27me1 is associated with active promoters (Barski et al., 2007). Their role remains somewhat elusive, however a recent paper showed that the PRC2 complex actually controls all three forms of H3K27 methylation (Ferrari et al., 2014). This paper supports previous findings about the distribution of H3K27me1/2: H3K27me1 was shown to positively affect transcription while H3K27me2 had a broad distribution and a role in silencing non-cell-type-specific enhancers (Ferrari et al., 2014).
But there is more to H3K27 than methylation. Acetylation of H3K27 has also been reported. Since a lysine residue cannot be both methylated and acetylated you would expect H3K27ac to be antagonistic to the repression of gene expression by H3K27me2/3. Indeed, data are showing that H3K27ac is associated with active transcription and antagonism of H3K27me3 regulated genes (Tie et al., 2009).
Histone H3K27 Additional Reading
This brief review succinctly summarizes much of what is known about the role of H3K27me in breast cancer. The role of H3K27me in regulation transcription is discussed, as well as data regarding H3K27me and EZH2 in breast cancers and how EZH2 represses BRCA1 function.
This review focuses on the role of PRC2 and H3K27me3 in the development of organs. It also gives a good overview of H3K27me3 mediated control of transcription.
- 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.
- Boyer, L.A., Plath, K., Zeitlinger, J., Brambrink, T., Medeiros, L.A., Lee, T.I., Levine, S.S., Wernig, M., Tajonar, A., Ray, M.K., et al. (2006). Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441, 349-353.
- Bracken, A.P., Dietrich, N., Pasini, D., Hansen, K.H., and Helin, K. (2006). Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev. 20, 1123-1136.
- Ferrari, K.J., Scelfo, A., Jammula, S., Cuomo, A., Barozzi, I., Stutzer, A., Fischle, W., Bonaldi, T., and Pasini, D. (2014). Polycomb-Dependent H3K27me1 and H3K27me2 Regulate Active Transcription and Enhancer Fidelity. Mol. Cell 53, 49-62.
- Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (2002). Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16, 2893-2905.
- 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.
- Tie, F., Banerjee, R., Stratton, C.A., Prasad-Sinha, J., Stepanik, V., Zlobin, A., Diaz, M.O., Scacheri, P.C., and Harte, P.J. (2009). CBP-mediated acetylation of histone H3 lysine 27 antagonizes Drosophila Polycomb silencing. Development 136, 3131-3141.