Histone H3 Lysine 4 Trimethylation, Lysine 27 Trimethylation, and Lysine 27 Acetylation Contribute to the Transcriptional Repression of Solute Carrier Family 47 Member 2 in Renal Cell Carcinoma

被引：12

作者：

Yu, Qinqin ^{[1
]}

Liu, Yanqing ^{[1
]}

Zheng, Xiaoli ^{[1
]}

Zhu, Qianying ^{[1
]}

Shen, Zhuowei ^{[1
]}

Wang, Hua ^{[2
]}

He, Huadong ^{[3
]}

Lin, Nengming ^{[3
]}

Jiang, Huidi ^{[1
]}

Yu, Lushan ^{[1
]}

Zeng, Su ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Drug Metab & Pharmaceut Anal, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou, Zhejiang, Peoples R China

[2] Canc Hosp Zhejiang Prov, Dept Urol, Hangzhou, Zhejiang, Peoples R China

[3] Hangzhou First Peoples Hosp, Dept Urol, Hangzhou, Zhejiang, Peoples R China

来源：

DRUG METABOLISM AND DISPOSITION | 2017年 / 45卷 / 01期

基金：

中国国家自然科学基金;

关键词：

EMBRYONIC STEM-CELLS; FUNCTIONAL-CHARACTERIZATION; PROGNOSTIC RELEVANCE; GENETIC-VARIANTS; HUMAN MULTIDRUG; METHYLATION; METFORMIN; MATE2-K; CANCER; PHARMACOKINETICS;

D O I：

10.1124/dmd.116.073734

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In recent years, finding effective biomarkers for identifying early stage cancer and predicating prognosis is crucial for renal cell carcinoma (RCC) diagnosis and treatment. In this study, a dramatic decrease of the solute carrier family 47 member 2 (SLC47A2) mRNA in RCC comparing with the paired adjacent nontumor tissues from patients at low Tumor Node Metastasis stage was observed. Thus, patients with SLC47A2 transcriptional repression are susceptible to RCC. Little is known about the regulation mechanism of SLC47A2. We found that it was a bivalent gene that was enriched with both histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 trimethylation (H3K27me3). Loss of mixed lineage leukemia 1 binding at the gene promoter caused decreased H3K4me3 enrichment and H3K4me3/H3K27me3 ratio, and subsequently repressed the expression of SLC47A2. These two epigenetic markers modulated the expression of SLC47A2 simultaneously, suggesting the regulation pattern for bivalent genes. Histone H3 lysine 27 acetylation also contributed to the expression of SLC47A2. An E2F1-histone deacetylase 10 complex catalyzed deacetylation of H3K27, then prevented the enrichment of H3K4me3, and finally reduced SLC47A2 expression. Consequently, the combined effect of all these factors determined SLC47A2 transcriptional repression in RCC tissues.

引用

页码：109 / 117

页数：9

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