UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells
UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells
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DOI：
10.1038/s41388-019-1032-y
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发表时间：
2020-01-01
期刊：
影响因子：
8
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
--
作者：
Taniue, Kenzui;Hayashi, Tomoatsu;Akiyama, Tetsu
表观遗传因子UHRF 1通过调节DNA甲基化和组蛋白修饰来调节转录，并且在增殖、发育和肿瘤发生中起关键作用。在这里，我们发现Wnt/c-Myc信号上调UHRF 1，这反过来又下调TUSC 3，一个候选的肿瘤抑制基因，经常在几种癌症中删除或下调。我们还表明，UHRF 1介导的下调TUSC 3是结肠癌细胞增殖所必需的。此外，我们证明了UHRF 1通过与甲基化的H3 K14相互作用，从而抑制组蛋白乙酰转移酶KAT 7对H3 K14的乙酰化，从而抑制TUSC 3的表达。我们的研究为UHRF 1-KAT 7介导的组蛋白甲基化/乙酰化调节在肿瘤细胞增殖中的意义以及在由Wnt/c-Myc信号转导控制的各种生物过程中的意义提供了证据。
The epigenetic factor UHRF1 regulates transcription by modulating DNA methylation and histone modification, and plays critical roles in proliferation, development, and tumorigenesis. Here, we show that Wnt/c-Myc signaling upregulates UHRF1, which in turn downregulates TUSC3, a candidate tumor suppressor gene that is frequently deleted or downregulated in several cancers. We also show that UHRF1-mediated downregulation of TUSC3 is required for the proliferation of colon cancer cells. Furthermore, we demonstrate that UHRF1 suppresses TUSC3 expression by interacting with methylated H3K14 and thereby suppressing the acetylation of H3K14 by the histone acetyltransferase KAT7. Our study provides evidence for the significance of UHRF1-KAT7-mediated regulation of histone methylation/acetylation in the proliferation of tumor cells and in a diverse set of biological processes controlled by Wnt/c-Myc signaling.