H4K20 if definitely the odd lysine out on the tail of H4. All the other lysines up until this point are acetylated and not methylated. H4K20 likes to go against the grain and is methylated but not acetylated. Like all lysine residues, H4K20 can be mono, di, or tri methylated. In the case of H4K20, these methylation states have different spatial disruptions and functions.
Histone H4K20 Fucntion
H4K20me1 is associated with transcriptional activation. The most highly transcribed group of genes tend to have H4K20me1 present in addition to the core group of modifications at active promoters (Wang et al., 2008). Only one enzyme, PR-Set7, catalyzes H4K20me1 (Beck et al., 2012). H4K20me1 is also important for cell cycle regulation. PR-Set7 levels oscillate during the cell cycle, and regulate chromatin condensation and mitotic progression (Wang et al., 2008).
H4K20me2 has similar but distinct genomic distribution and roles as H4K20me1. The dimethylation is believed to be important for cell cycle control, particularly for marking points of origin for DNA replication (Kuo et al., 2012). H4K20me2 is also important in the DNA damage response (Botuyan et al., 2006). Specially, it is bound by 53BP1 which is a central DNA repair factor.
H4K20me3 serves a much different function that the other two methylation states. In general, H4K20me3 is associated with repression of transcription when present at promoters (Wang et al., 2008). H4K20me3 also appears to be important for the silencing of repetitive DNA and transposons (Schotta et al., 2004). These results may explain why the loss of H4K20me3 has be identified as a hallmark of cancer (Fraga et al., 2005). Together with reduction of H4K16ac, loss of H4K20me3 is a near universal characteristic of human cancers.
Histone H4K20 Additional Reading
This paper and accompanying summary examine the role of H4K20me1 in WNT signalling, an important pathway involved in cellular proliferation.
This recent review is devoted to examining the roles of all H4K20 methylations. The review goes through many biological processes and lists details of how the three methylation states are involved in each.
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- Botuyan, M.V., Lee, J., Ward, I.M., Kim, J.E., Thompson, J.R., Chen, J., and Mer, G. (2006). Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell 127, 1361-1373.
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- Kuo, A.J., Song, J., Cheung, P., Ishibe-Murakami, S., Yamazoe, S., Chen, J.K., Patel, D.J., and Gozani, O. (2012). The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome. Nature 484, 115-119.
- Schotta, G., Lachner, M., Sarma, K., Ebert, A., Sengupta, R., Reuter, G., Reinberg, D., and Jenuwein, T. (2004). A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 18, 1251-1262.
- Wang, Z., Zang, C., Rosenfeld, J.A., Schones, D.E., Barski, A., Cuddapah, S., Cui, K., Roh, T.Y., Peng, W., Zhang, M.Q., and Zhao, K. (2008). Combinatorial patterns of histone acetylations and methylations in the human genome. Nat. Genet. 40, 897-903.