We began by noting that proteomics predictions estimate that there are considerably more proteins in a cell than what are encoded by the DNA. In this review we touched on a number of modifications known to be important for regulating chromatin structure and transcription. However, we limited our discussion to just a handful of modifications on only a few proteins. With the rapid evolution of high-throughput proteomics techniques, our understanding of the extent of protein modification will undoubtedly increase in the next few years. Deciphering the roles of newfound modifications will become more complex as the number of modified proteins increases. Perhaps, understanding the complex networks of protein modifications is the key to understanding how transcription integrates with other cell processes such as mRNA processing, cell-cycle regulation, and signaling events.
Histone tails seem to be the richest sources of protein modifications in cells. This is likely due to their essential roles in maintaining chromatin structure. Are there other modification-rich proteins that have been largely overlooked? Preliminary evidence suggests there are. RNA-binding proteins as well as ribosomal proteins are known to be heavily methylated [186
]. What are the roles of methylation in mRNA processing or translation? Structural proteins such as myelin basic protein are decorated with a diverse set of modifications that seem to play essential roles in neurodegenerative disorders [187
]. How do modifications of these proteins regulate protein function? Perhaps the most complex modifications are manifest outside the cell. Researchers have spent decades studying how glycosylation patterns on proteins dictate how a cell interacts with its environment [188
]. Deciphering glycosylation is key to understanding a number of today's biomedical problems including cancer metastasis and cell differentiation [189
Protein modifications will likely continue to play a starring role in future stories of chromatin structure and gene regulation. As more modifications are identified, it is likely that these PTMs will be key players in the regulation of gene expression as well as other biological processes in the cell. In that respect, previous and current work on histone modifications will serve as a roadmap for deciphering the function of protein modifications in biology.