Lateral Thinking: How Histone Modifications Regulate Gene Expression

The DNA of each cell is wrapped around histone octamers, forming so-called ‘nucleosomal core particles’. These histone proteins have tails that project from the nucleosome and many residues in these tails can be post-translationally modified, influencing all DNA-based processes, including chromatin compaction, nucleosome dynamics, and transcription. In contrast to those present in histone tails, modifications in the core regions of the histones had remained largely uncharacterised until recently, when some of these modifications began to be analysed in detail. Overall, recent work has shown that histone core modifications can not only directly regulate transcription, but also influence processes such as DNA repair, replication, stemness, and changes in cell state. In this review, we focus on the most recent developments in our understanding of histone modifications, particularly those on the lateral surface of the nucleosome. This region is in direct contact with the DNA and is formed by the histone cores. We suggest that these lateral surface modifications represent a key insight into chromatin regulation in the cell. Therefore, lateral surface modifications form a key area of interest and a focal point of ongoing study in epigenetics.

TrendsThe globular domains of histones represent the emerging front of histone modification research.Modifications in the globular domains of histones can directly affect transcription and nucleosome stability.Many globular domain modifications also have roles in the DNA damage response, stemness, leukaemia and cell differentiation.Novel modifications, such as arginine methylation, are also present in this region and can directly affect the compaction of the DNA coating the nucleosome.