H2A is often overlooked, but H2B often forgotten completely. H2B forms a (H2A-H2B)-2 tetramer. This tetramer and it’s component dimers are easily exchanged in and out of the nucleosome compared to H3 and H4, meaning that the modifications on H2A and H2B are less likely to be maintained in chromatin (Kimura and Cook, 2001). This may be part of the reason modifications on H2A/H2B have been less studied than H3 and H4by epigenetics resarchers. However, many scientists recognize the potential impact modifications on H2B can have on chromatin dynamics.
Histone H2B Modifications
Like the other histones, H2B undergoes several N-terminal tail modifications. These include acetylation at K5, K12, K15, and K20 and phosphorylation at S14 in humans (Allis et al., 2007; Cheung et al., 2003). The exact role of these modifications are not yet understood. It is clear however that certain acetylations of H2A and H2B group with known patterns of H3 and H4 acetylations (Liu et al., 2005). This implies that H2A and H2B modifications contribute to transcription, but may not provide unique information.
Both H2A and H2B are distinct from H3 and H4 in that they can be monoubiquitinated. Ubiquitination is a much larger group than other posttranslational modifications, and thus has important steric consequences for the nucleosome. Unlike H2A, monoubiquitination of H2B appears have a positive effect on transcription. H2B monoubiquitination (H2Bub1) occurs at K120 in mammals. Ubiquitination at this site is carried out by the ubiquitin RNF20 and RNF40 ligases (Zhu et al., 2005). H2Bub1 is associated with the ORFs of actively transcribed genes and correlates with gene expression level, suggesting an important role in transcriptional elongation (Minsky et al., 2008). H2Bub1 is required for the transcriptional activators H3K4 di and tri methylation to be deposited (Shahbazian et al., 2005). However, H2Bub1 is also associated with blocking transcription of certain genes (Shema et al., 2008). These seemingly contradictory results suggest a complex role for H2Bub1 that is yet to be fully characterized. Beyond its role in transcription, H2Bub1 also appears to be critical for DNA damage responses and acts as a tumour suppressor and thus may be important in cancer (Johnsen, 2012).
Histone H2B Additional reading:
This is an excellent review on individual H2A and H2B post-translational modifications and their known roles.
This review gives a look at H2A and H2B ubiquitination and is consequences. The authors pay particular focus to the establishment of the marks, but also discuss the biological impact.
Histone H2B References
- Allis, C.D., Berger, S.L., Cote, J., Dent, S., Jenuwien, T., Kouzarides, T., Pillus, L., Reinberg, D., Shi, Y., Shiekhattar, R., et al. (2007). New nomenclature for chromatin-modifying enzymes. Cell 131, 633-636.
- Cheung, W.L., Ajiro, K., Samejima, K., Kloc, M., Cheung, P., Mizzen, C.A., Beeser, A., Etkin, L.D., Chernoff, J., Earnshaw, W.C., and Allis, C.D. (2003). Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell 113, 507-517.
- Johnsen, S.A. (2012). The enigmatic role of H2Bub1 in cancer. FEBS Lett. 586, 1592-1601.
- Kimura, H., and Cook, P.R. (2001). Kinetics of core histones in living human cells: little exchange of H3 and H4 and some rapid exchange of H2B. J. Cell Biol. 153, 1341-1353.
- Liu, C.L., Kaplan, T., Kim, M., Buratowski, S., Schreiber, S.L., Friedman, N., and Rando, O.J. (2005). Single-nucleosome mapping of histone modifications in S. cerevisiae. PLoS Biol. 3, e328.
- Minsky, N., Shema, E., Field, Y., Schuster, M., Segal, E., and Oren, M. (2008). Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat. Cell Biol. 10, 483-488.
- Shahbazian, M.D., Zhang, K., and Grunstein, M. (2005). Histone H2B ubiquitylation controls processive methylation but not monomethylation by Dot1 and Set1. Mol. Cell 19, 271-277.
- Shema, E., Tirosh, I., Aylon, Y., Huang, J., Ye, C., Moskovits, N., Raver-Shapira, N., Minsky, N., Pirngruber, J., Tarcic, G., et al. (2008). The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev. 22, 2664-2676.
- Zhu, B., Zheng, Y., Pham, A.D., Mandal, S.S., Erdjument-Bromage, H., Tempst, P., and Reinberg, D. (2005). Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation. Mol. Cell 20, 601-611.