Epigenetic inheritance mediated by histone lysine methylation: maintaining transcriptional states without the precise restoration of marks?

Abstract

‘Epigenetics’ has been defined as the study of ‘mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence’. Chromatin modifications are major carriers of epigenetic information that both reflect and affect the transcriptional states of underlying genes. Several histone modifications are key players that are responsible for classical epigenetic phenomena. However, the mechanisms by which cells pass their histone modifications to daughter cells through mitotic division remain to be unveiled. Here, we review recent progress in the field and conclude that epigenetic modifications are not precisely maintained at a near-mononucleosome level of precision. We also suggest that transcription repression may be maintained by a buffer system that can tolerate a certain degree of fluctuation in repressive histone modification levels. This buffer system protects the repressed genes from potential improper derepression triggered by chromatin modification-level fluctuation resulting from cellular events, such as the cell-cycle-dependent dilution of the chromatin modifications and local responses to environmental cues.