Abstract
Genomic DNA in the eukaryotic cell nucleus is present in the form of chromatin. Histones are the principal protein component of chromatin, and their post-translational modifications play important roles in regulating the structure and function of chromatin and thereby in determining cell development and disease. An understanding of how histone modifications translate into downstream cellular events is important from both developmental and therapeutic perspectives. However, biochemical studies of histone modifications require access to quantities of homogenously modified histones that cannot be easily isolated from natural sources or generated by enzymatic methods. In the past decade, chemical synthesis has proven to be a powerful tool in translating the language of histone modifications by providing access to uniformly modified histones and by the development of stable analogues of thermodynamically labile modifications. This Review highlights the various synthetic and semisynthetic strategies that have enabled biochemical and biophysical characterization of site-specifically modified histones.
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