H3K36 is like a fine wine: complex, intriguing, and an active source of interest among researchers. The modifications occurring at H3K36 are very diverse and don’t share much similarity with each other. They have roles in many important biological processes. H3K36 has functionally relevant acetylation and methylation states. H3K36 acetylation has been relatively recently characterized. Its distribution pattern in the genome is similar to other common H3 acetylations. Similarly, it plays a role in transcriptional activation (Morris et al., 2007).
Histone H3K36 Modifications
The mono, di, and trimethylation states differ from each other in their distributions and functional roles. There is a shift from mono, to di, to tri methylation from the promoter to the 3’ end active genes (Barski et al., 2007). It has been shown in yeast that H3K36me3 is deposited on histones as they are displaced by RNA polymerase II (RNAPII) during transcription. H3K36me3 then serves as a mark for HDACs to bind and deacetylate the histones, preventing run-away transcription in the wake of RNAPII (Carrozza et al., 2005; Joshi and Struhl, 2005). Evidence suggests this may also be true in humans; however, H3K9 is used in conjunction with H3K36 to repressive aberrant transcription (Bartke et al., 2010).
Histone H3K36 Function
H3K36me3 may also be involved in defining exons. Exons are enriched in nucleosomes in general, but these nucleosomes are also enriched in certain histone modifications including H3K79, H4K20, and especially H3K36me3 (Schwartz et al., 2009). It is believed that this pattern influences alternative splicing in some way, perhaps by signalling effector proteins to mark particular exons for inclusion in the final transcript as they exit the RNAPII complex (Luco et al., 2010).
The role of H3K36me1 remains unclear; however, H3K36me2 is relatively well characterised. For instance, H3K36me2 has a role in double-strand break repair. H3K36me2 is deposited near the double-strand breaks early, and then serves to recruit early repair factors such as NBS1 and Ku70 (Fnu et al., 2011).
Histone H3K36 Additional Reading
This is an excellent review on H3K36 methylations and their known roles. The first half focuses on the proteins involved in creating and reading H3K36 methylations. The review also addresses the known roles for different methylation states.
This review looks at the dynamics of mRNA splicing and pays particular focus to the role of H3K36me in the process.
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- Bartke, T., Vermeulen, M., Xhemalce, B., Robson, S.C., Mann, M., and Kouzarides, T. (2010). Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell 143, 470-484.
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- Fnu, S., Williamson, E.A., De Haro, L.P., Brenneman, M., Wray, J., Shaheen, M., Radhakrishnan, K., Lee, S.H., Nickoloff, J.A., and Hromas, R. (2011). Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc. Natl. Acad. Sci. U. S. A. 108, 540-545.
- Joshi, A.A., and Struhl, K. (2005). Eaf3 chromodomain interaction with methylated H3-K36 links histone deacetylation to Pol II elongation. Mol. Cell 20, 971-978.
- Luco, R.F., Pan, Q., Tominaga, K., Blencowe, B.J., Pereira-Smith, O.M., and Misteli, T. (2010). Regulation of alternative splicing by histone modifications. Science 327, 996-1000.
- Morris, S.A., Rao, B., Garcia, B.A., Hake, S.B., Diaz, R.L., Shabanowitz, J., Hunt, D.F., Allis, C.D., Lieb, J.D., and Strahl, B.D. (2007). Identification of histone H3 lysine 36 acetylation as a highly conserved histone modification. J. Biol. Chem. 282, 7632-7640.
- Schwartz, S., Meshorer, E., and Ast, G. (2009). Chromatin organization marks exon-intron structure. Nat. Struct. Mol. Biol. 16, 990-995.