G9a-dependent histone methylation can be induced in G1 phase of cell cycle

Abstract

Epigenetic information (epigenome) on chromatin is crucial for the determination of cellular identity and for the expression of cell type-specific biological functions. The cell type-specific epigenome is maintained beyond replication and cell division. Nucleosomes of chromatin just after DNA replication are a mixture of old histones with the parental epigenome and newly synthesized histones without such information. The diluted epigenome is mostly restored within one cell cycle using the epigenome on the parental DNA and nucleosomes as replication templates. However, many important questions about the epigenome replication process remain to be clarified. In this study, we investigated the model system comprising of dimethylated histone H3 lysine 9 (H3K9me2) and its regulation by the lysine methyltransferase G9a. Using this epigenome model system, we addressed whether H3K9me2 can be induced in specific cell cycle stages, especially G1. Using cell cycle-specific degrons, we achieved G1 or late G1-to M phases specific accumulation of exogenous G9a in G9a deficient cells. Importantly, global levels of H3K9me2 were significantly recovered by both cell types. These data indicate that H3K9me2 may be plastic and inducible, even in the long-living, terminally-differentiated, post-mitotic, G0-G1 cell population in vivo. This knowledge is valuable in designing epigenome-manipulation-based treatments for diseases.