Title:Recent Advance in Epigenetics - Application to The Regulation of Osteoclast Differentiation
Volume: 8
Issue: 2
Author(s): Tetsuro Yasui, Jun Hirose, Hiroyuki Aburatani and Sakae Tanaka
Affiliation:
Keywords:
Epigenetics, Histone Modification, Jmjd3, Osteoclast differentiation.
Abstract: Osteoclasts are primary cells for bone resorption, and their differentiation is tightly regulated by receptor activator
of nuclear factor kappa B ligand (RANKL) and a transcription factor nuclear factor-activated T cells (NFAT) c1.
Recent studies have uncovered that the epigenetic regulation such as DNA methylation, histone methylation and acetylation,
and micro RNAs play a critical role in cell differentiation. In particular, the expression of key developmental genes
tends to be tightly regulated by trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3). Several reports
have been proposed regarding the epigenetic regulation of osteoclast differentiation including this specific histone
modification change. RANKL-induced NFATc1 expression is associated with the demethylation of H3K27me3 in osteoclast
precursors. Jumonji domain containing-3 (Jmjd3), a H3K27 demethylase, is induced in murine bone marrow-derived
macrophages in response to RANKL stimulation, and supposedly plays a critical role in the demethylation of H3K27me3
in the Nfatc1 gene and osteoclast differentiation.
