The Histone Code

Abstract

Post-translational modifications of histones are frequent and important epigenetic signals that control many biological processes, such as cellular differentiation in the context of embryogenesis. Acetylations and methylations of lysines in histone tails are understood best and may be most important epigenetic marks, but there are also a number of other acylations, such as formylation, propionylation, malonylation, crotonylation, butyrylation, succinylation, glutarylation and myristoylation, the functional impact of which is far less understood. In addition, there are phosphorylations at tyrosines, serines, histidines and threonines, ADP ribosylations at lysines and glutamates, citrullinations of arginines, hydroxylations of tyrosines, glycations of serines and threonines as well as sumoylations and ubiquitinations of lysines. All together these modifications form a collection of signals, referred to as the histone code, that mark genomic regions and pass information to chromatin modifiers and other nuclear proteins. The collection of histone modification patterns from various human cell lines and primary tissues, as provided by ENCODE, Roadmap Epigenomics and IHEC, provide a genome-wide basis of the histone code and its impact. Furthermore, signals from histone modifications combine with information provided by DNA methylations and post-translational modifications of non-histone proteins, such as transcription factors.

In this chapter, we will discuss the respective chemical and structural basis of different types of histone modifications and will present results from their genome-wide profiling. Finally, we will analyze the combination of histone modifications with DNA methylation and post-translational modifications of non-histone proteins.