H4K5 is the closest lysine residue to the N-terminal tail of histone H4. Histone H4 forms a strong tetramer with histone H3. Like histone H3, H4 has a long N-terminal tail that is subject to various acetylations and methylations that are associated with many cellular processes. H4 modifications are not as well characterized as H3. H4 has much less sequence variation than the other histones across species; it seem to be structurally restrained by evolution likely due to important function (Thatcher and Gorovsky, 1994).
Histone H4K5 Modifications
H4K5 has not been shown to be methylated, there is only data on its acetylation. Like all acetylations, H4K5ac is catalyzed by several enzymes, including Tip60 and CBP/p300 proteins in mammals (Kimura and Horikoshi, 1998; Schiltz et al., 1999). CBP/p300 are important transcriptional activators that serve to open transcriptional start site chromatin by acetylating histones, and form a complex with the basal transcriptional machinery.
Histone H4K5 Function
H4K5ac has also been implicated in epigenetic bookmarking. Epigenetic bookmarking the name given to a proposed process that allows gene expression patterns to be faithfully passed to daughter cells through mitosis. Important cell-type specific genes are marked in some way that prevents them from being compacted during mitosis and ensures their rapid transcription. H4K5ac has been implicated as one such mark (Zhao et al., 2011). Zhao et al. found that transcriptional activity during interphase causes acetylation of H4K5 and H4K12 which are passed through mitosis. These marks then recruit BRD4 which de-compacts the local chromatin environment and permits transcriptional activation. Similarly, other papers have found that H4K5ac can serve as a primer for rapid transcription in other contexts. H4K5ac appears to prime activity-dependent genes expressed during learning (Park et al., 2013). The mark may permit the rapid expression of certain genes required during the learning process.
Histone H4K5 Additional Reading
This review focuses more on H4 modifications than most others. It is a great resource for primary literature on the role of different H4 acetylations, as well as H4 and the other histones in general. Definitely a must read.
This review gives an overview of epigenetic inheritance in general, but pays specific attention to so called “bookmarking”. The review give many different examples of biological processes involved, as well as different mechanisms of bookmarking.
References
- Kimura, A., and Horikoshi, M. (1998). Tip60 acetylates six lysines of a specific class in core histones in vitro. Genes Cells 3, 789-800.
- Park, C.S., Rehrauer, H., and Mansuy, I.M. (2013). Genome-wide analysis of H4K5 acetylation associated with fear memory in mice. BMC Genomics 14, 539-2164-14-539.
- Schiltz, R.L., Mizzen, C.A., Vassilev, A., Cook, R.G., Allis, C.D., and Nakatani, Y. (1999). Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates. J. Biol. Chem. 274, 1189-1192.
- Thatcher, T.H., and Gorovsky, M.A. (1994). Phylogenetic analysis of the core histones H2A, H2B, H3, and H4. Nucleic Acids Res. 22, 174-179.
- Zhao, R., Nakamura, T., Fu, Y., Lazar, Z., and Spector, D.L. (2011). Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation. Nat. Cell Biol. 13, 1295-1304.