UHRF1-KAT7-mediated regulation of TUSC3 expression via histone methylation/acetylation is critical for the proliferation of colon cancer cells

被引：33

作者：

Taniue, Kenzui ^{[1
]}

Hayashi, Tomoatsu ^{[1
]}

Kamoshida, Yuki ^{[1
]}

Kurimoto, Akiko ^{[1
,2
]}

Takeda, Yasuko ^{[1
]}

Negishi, Lumi ^{[1
]}

Iwasaki, Kei ^{[1
]}

Kawamura, Yoshifumi ^{[3
]}

Goshima, Naoki ^{[4
]}

Akiyama, Tetsu ^{[1
]}

机构：

[1] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Mol & Genet Informat, Bunkyo Ku, Tokyo, Japan

[2] Daiichi Sankyo Co Ltd, Oncol Res Labs, Shinagawa Ku, Tokyo, Japan

[3] Japan Biol Informat Consortium, Koto Ku, Tokyo, Japan

[4] Natl Inst Adv Ind Sci & Technol, Mol Profiling Res Ctr Drug Discovery, Koto Ku, Tokyo, Japan

来源：

ONCOGENE | 2020年 / 39卷 / 05期

关键词：

DNA METHYLATION; PROMOTES PROLIFERATION; BURKITT-LYMPHOMA; STRUCTURAL BASIS; GENE-REGULATION; MYST FAMILY; STEM-CELLS; SRA DOMAIN; UHRF1; PROTEIN;

D O I：

10.1038/s41388-019-1032-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1018 / 1030

页数：13

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