Epigenetic regulation of osteoclast differentiation: Possible involvement of Jmjd3 in the histone demethylation of Nfatc1
Epigenetic regulation of osteoclast differentiation: Possible involvement of Jmjd3 in the histone demethylation of Nfatc1
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DOI：
10.1002/jbmr.464
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发表时间：
2011-11
影响因子：
6.2
通讯作者：
T. Yasui;J. Hirose;S. Tsutsumi;Kozo Nakamura;H. Aburatani;Sakae Tanaka
中科院分区：
文献类型：
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作者：
T. Yasui;J. Hirose;S. Tsutsumi;Kozo Nakamura;H. Aburatani;Sakae Tanaka
基因表达受表观遗传机制如组蛋白乙酰化和甲基化控制，最近的研究表明，关键的发育步骤受组蛋白H3赖氨酸4（H3 K4 me 3）和赖氨酸27（H3 K27 me 3）的三甲基化调节。使用ChIP测序技术结合真实的时间PCR，我们在这里证明了在骨髓源性巨噬细胞（BMSCs）的Nfatc 1基因中观察到的H3 K27 me 3在成熟破骨细胞中显著减少。含Jumonji结构域3（Jmjd 3）是一种H3 K27脱甲基酶，在骨髓源性巨噬细胞中和核因子活化T细胞（NFAT）c1的转录起始位点（TSS）附近诱导，以响应核因子-κB配体（RANKL）受体激活剂刺激。通过短发夹RNA对Jmjd 3基因进行基因沉默，减少了Nfatc 1 TSS处H3 K27 me 3的去甲基化，并抑制了RANKL诱导的破骨细胞生成。这些结果表明，Jmjd 3引起的Nfatc 1基因座中H3 K27 me 3的去甲基化在RANKL诱导的破骨细胞分化中起关键作用。© 2011美国骨与矿物质研究学会
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