Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Genes Dev. 2010 Mar 1;24(5):432-7. doi: 10.1101/gad.1864410.
Methylation of histone H3 Lys 9 and Lys 27 (H3K9 and H3K27) is associated with transcriptional silencing. Here we show that KDM7, a JmjC domain-containing protein, catalyzes demethylation of both mono- or dimethylated H3K9 and H3K27. Inhibition of KDM7 orthologs in zebrafish resulted in developmental brain defects. KDM7 interacts with the follistatin gene locus, and KDM7 depletion in mammalian neuronal cells suppressed follistatin gene transcription in association with increased levels of dimethylated H3K9 and H3K27. Our findings identify KDM7 as a dual demethylase for H3K9 and H3K27 that functions as an eraser of silencing marks on chromatin during brain development.
组蛋白 H3 赖氨酸 9 和赖氨酸 27(H3K9 和 H3K27)的甲基化与转录沉默有关。在这里,我们表明 JmjC 结构域蛋白 KDM7 催化单甲基化或二甲基化 H3K9 和 H3K27 的去甲基化。斑马鱼中 KDM7 同源物的抑制导致发育性脑缺陷。KDM7 与卵泡抑素基因座相互作用,哺乳动物神经元细胞中 KDM7 的耗竭与二甲基化 H3K9 和 H3K27 水平的增加与抑制卵泡抑素基因转录相关。我们的研究结果表明 KDM7 是 H3K9 和 H3K27 的双去甲基酶,在大脑发育过程中作为染色质上沉默标记的橡皮擦。