H4K8 is another lysine on that tail of histone H4 that doesn’t get a lot of attention. Like the others in this group, it is only known to be acetylated, and has not been shown to be methylated as of yet. This group of lysines are known to act as transcriptional activators (Wang et al., 2008). These lysines are also an excellent example of the histone code hypothesis in action.
Histone H4K8 Function
The histone code hypothesis proposes that different histone modifications code for different chromatin conformations, and that these modifications act in a coordinated manner to influence biological processes (Turner, 2000). The hypothesis entails that modifications have definable roles in the cell that are best understood by examining the modifications in concert. Wang et al. (2008) present a comprehensive examination of these patterns and propose many relationships between the modifications (Wang et al., 2008). The authors found that H4K8ac is part of a “backbone” of 17 modifications that occupy most active promoters. Additional modifications can be added to the backbone group to modulate promoter activity to fine-tune the expression level. This study also found that H4K8ac was found more often in active promoters and transcribed regions than others in the backbone group which were found more at transcriptional start sites.
H4K8ac is catalyzed and read by a slightly different group of enzymes than other H4 lysines. Several acetyltransferases catalyze H4K8ac. In yeast, the acetyltransferase GCN5 acts on H4K8. GCN5 is part of the SAGA coactivator complex (Larschan and Winston, 2001). Interestingly, the broad-acting CBP/p300 proteins do not appear to read H4K8 (Agalioti et al., 2002). H4K8 does bind the SWI/SNF complex however (Agalioti et al., 2002). These data are significant because CBP/p300 interact with the RNAPII initiation complex, while SWI/SNF interact with the elongation complex (Cho et al., 1998). This suggests that H4K8ac is involved in transcriptional elongation, rather than initiation.
Histone H4K8 Additional Reading
This is an excellent recent review on not only evidence for this histone code hypothesis, but also evidence against it. The author also tries to reconcile the conflicting evidence in the context of biological
This review looks in detail at the proteins involved in RNA polymerase II elongation. It briefly discusses the role of H4 acetylation in protein recruitment, but its focus is mostly on the stages, details, and proteins involved in the process.
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- Larschan, E., and Winston, F. (2001). The S. cerevisiae SAGA complex functions in vivo as a coactivator for transcriptional activation by Gal4. Genes Dev. 15, 1946-1956.
- Turner, B.M. (2000). Histone acetylation and an epigenetic code. Bioessays 22, 836-845.
- 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.