ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes.
ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes.
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ZMYND8 读取双组蛋白标记 H3K4me1-H3K14ac 以拮抗转移相关基因的表达
DOI：
10.1016/j.molcel.2016.06.035
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发表时间：
2016-08-04
期刊：
影响因子：
16
通讯作者：
Lee MG
中科院分区：
文献类型：
--
作者：
Li N;Li Y;Lv J;Zheng X;Wen H;Shen H;Zhu G;Chen TY;Dhar SS;Kan PY;Wang Z;Shiekhattar R;Shi X;Lan F;Chen K;Li W;Li H;Lee MG
组蛋白乙酰化，包括乙酰化H3K14 (H3K14ac)，通常与基因激活有关。单甲基化组蛋白H3赖氨酸4 （H3K4me1）与其他基因激活标记一起表示活性基因。与通常的H3K14ac和H3K4me1的基因激活功能不同，我们在这里发现了双组蛋白修饰标记H3K4me1-H3K14ac被ZMYND8（也称为RACK7）识别，并能起抵消基因表达的作用。我们发现ZMYND8是H3K4去甲基化酶JARID1D的转录共抑制因子。ZMYND8可拮抗转移相关基因的表达，敲低ZMYND8可增加体内和体外的细胞侵袭性。ZMYND8中的植物同源域（PHD）和溴域盒介导了ZMYND8对H3K4me1-H3K14ac和H3K4me0-H3K14ac的组合识别。这些发现揭示了H3K4me1-H3K14ac在降低基因表达中的意想不到的作用，并揭示了一个以前未知的转移抑制表观遗传机制，其中ZMYND8的PHD-Bromo磁带将H3K4me1-H3K14ac与转移相关基因的下调结合在一起。
Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating can function of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and can function to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonized the expression of metastasis-linked genes, and its knockdown increased the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediated the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a previously unknown metastasis-suppressive epigenetic mechanism in which ZMYND8’s PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes.