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Epigenetic regulation of osteoclast differentiation: Possible involvement of Jmjd3 in the histone demethylation of Nfatc1
Author(s) -
Yasui Tetsuro,
Hirose Jun,
Tsutsumi Shuichi,
Nakamura Kozo,
Aburatani Hiroyuki,
Tanaka Sakae
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.464
Subject(s) - h3k4me3 , nfat , demethylase , histone methylation , histone h3 , rankl , histone , biology , epigenetics , microbiology and biotechnology , ezh2 , chemistry , cancer research , activator (genetics) , gene expression , dna methylation , transcription factor , genetics , receptor , gene , promoter
Gene expression is controlled by epigenetic mechanisms such as histone acetylation and methylation, and recent studies have revealed that key developmental steps are regulated by the trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3). Using ChIP sequencing technology combined with real‐time PCR, we here demonstrate that the H3K27me3 observed in the Nfatc1 gene in bone marrow–derived macrophages (BMMs) was markedly reduced in mature osteoclasts. Jumonji domain‐containing 3 (Jmjd3), a H3K27 demethylase, was induced in bone marrow–derived macrophages and in the vicinity of the transcription start site (TSS) of nuclear factor–activated T cells (NFAT) c1 in response to receptor activator of nuclear factor‐κB ligand (RANKL) stimulation. Gene silencing of the Jmjd3 gene by short hairpin RNA reduced demethylation of H3K27me3 at the TSS of Nfatc1 and suppressed RANKL‐induced osteoclastogenesis. These results suggest that the demethylation of H3K27me3 in the Nfatc1 gene locus by Jmjd3 plays a critical role in RANKL‐induced osteoclast differentiation. © 2011 American Society for Bone and Mineral Research