Credit: Reprinted with permission from Elsevier.

Turnover and exchange of histones and their variants has long been believed to be negligible in postreplicative cells. This view has been challenged by recent studies in postmitotic neurons (for example, Neuron 87, 77–94, 2015), in which histone-variant exchange was observed during neuronal activity–dependent gene expression. Now, Hajkova and colleagues show that histone-variant exchange also occurs during mouse oogenesis, even in the absence of transcription (Mol. Cell. doi:10.1016/j.molcel.2015.10.010, 5 November 2015).

Postnatal mammalian oocytes undergo several developmental transitions in the absence of DNA replication, thus making oogenesis an ideal system to study replication-independent histone dynamics. Using this system, the authors found that microinjection of mRNA for Flag-tagged histone H3.3, but not Flag-tagged canonical histones H3.1 and H3.2, led to incorporation of the histone into the chromatin of growing oocytes. Unexpectedly, new H3.3 incorporation was also seen in transcriptionally inert germinal vesicle–stage oocytes (pictured). Oocyte-specific deletion of Hira, a histone chaperone required for H3.3 incorporation, abolished incorporation of microinjected H3.3 and led to chromatin decondensation accompanied by signs of DNA damage. Single-cell RNA and bisulfite sequencing showed that Hira is necessary for normal gene expression and de novo DNA methylation during oocyte development.

This study provides further evidence that histone replacement in postmitotic cells is physiologically important. Such exchange could be important for cell type–specific transcription and plasticity in response to external cues as well as for maintaining genome integrity. It will be interesting to determine whether H3.3 exchange also occurs in other nonproliferating cells.