KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development
KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development
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DOI：
10.1101/gad.1864410
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发表时间：
2010-03-01
影响因子：
10.5
通讯作者：
Nakayama, Keiichi I.
中科院分区：
文献类型：
--
作者：
Tsukada, Yu-ichi;Ishitani, Tohru;Nakayama, Keiichi I.
组蛋白H3Lys 9和Lys 27(H3K9和H3K27)的甲基化与转录沉默有关。在这里，我们证明了KDM7，一个含有JmjC结构域的蛋白质，催化单甲基化或二甲基化的H3K9和H3K27的去甲基化。抑制斑马鱼中的KDM7同源基因会导致大脑发育缺陷。KDM7与卵泡抑素基因位点相互作用，哺乳动物神经细胞中KDM7的缺失抑制了卵泡抑素基因的转录，同时增加了甲基化的H3K9和H3K27的水平。我们的发现确定KDM7是H3K9和H3K27的双重去甲基酶，在大脑发育过程中起到消除染色质上沉默标记的作用。
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.