Histone methylation: a dynamic mark in health, disease and inheritance

Abstract

Organisms require an appropriate balance of stability and reversibility in gene expression programmes to maintain cell identity or to enable responses to stimuli; epigenetic regulation is integral to this dynamic control. Post-translational modification of histones by methylation is an important and widespread type of chromatin modification that is known to influence biological processes in the context of development and cellular responses. To evaluate how histone methylation contributes to stable or reversible control, we provide a broad overview of how histone methylation is regulated and leads to biological outcomes. The importance of appropriately maintaining or reprogramming histone methylation is illustrated by its links to disease and ageing and possibly to transmission of traits across generations.

Figure 1. Models for inheritance of histone methylation marks

a) Semiconservative replication of histones (and their marks). The half of the histone octamer, which is inherited (and therefore appropriately marked), could inform the cell machinery to mark the newly added histone proteins. b) Entire histone octamers are segregated to each of the daughter strands in alternating fashion and the newly synthesized histones could be informed by the neighboring parental histone marks. c) DNA methylation acts as a signal to methylate specific new histones. d) Deposition of histones containing pre-existing modifications. Previously labeled free histones could be recruited to important sites where an epigenetic memory is needed and integrated into newly synthesized DNA.