The Roles of Histone Demethylase Jmjd3 in Osteoblast Differentiation and Apoptosis

Abstract

Posttranslational modifications including histone methylation regulate gene transcription through directly affecting the structure of chromatin. Trimethylation of histone 3 lysine 27 (H3K27me3) is observed at the promoters of a wide variety of important genes, especially for mammalian development, and contributes to gene silencing. Demethylase Jumonji domain-containing 3 (Jmjd3) catalyzes the transition of H3K27me3 to H3K27me1, therefore from a repressive to an active status of gene expression. Jmjd3 plays important roles in cell differentiation, inflammation, and tumorigenesis by targeting distinct transcription factors. In this review, we summarize the pivotal roles of Jmjd3 in maintaining skeletal homeostasis through regulating osteoblast differentiation, maturation, and apoptosis.

Keywords: H3K27me3; Jmjd3; bone formation; osteoblast apoptosis; osteoblast differentiation.

Figure 1

Jmjd3 regulates osteoblast differentiation through transcription factors Runx2 and Osterix. BMP-2 induces Jmjd3 expression and translocation into the nucleus, where the level of H3K27me3 on the promoter regions of Runx2 and Osterix decreases by demethylation. Thus, this further promotes Msx-2 and Dlx-5 to approach to the binding sites of these promoters, resulting in the up-regulations of Runx2 and Osterix.