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首页> 外文期刊>Carcinogenesis >A time-series analysis of altered histone H3 acetylation and gene expression during the course of MMA(III)-induced malignant transformation of urinary bladder cells
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A time-series analysis of altered histone H3 acetylation and gene expression during the course of MMA(III)-induced malignant transformation of urinary bladder cells

机译：改变组蛋白H3乙酰化和基因表达在MMA（III）的过程中的时间序列分析 - 诱导尿膀胱细胞的恶性转化

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摘要

Our previous studies have shown that chronic exposure to low doses of monomethylarsonous acid (MMA(III)) causes global histone acetylation dysregulation in urothelial cells (UROtsa cells) during the course of malignant transformation. To reveal the relationship between altered histone acetylation patterns and aberrant gene expression, more specifically, the carcinogenic relevance of these alterations, we performed a time-course analysis of the binding patterns of histone 3 lysine 18 acetylation (H3K18ac) across the genome and generated global gene-expression profiles from this UROtsa cell malignant transformation model. We showed that H3K18ac, one of the most significantly upregulated histone acetylation sites following MMA(III) exposure, was enriched at gene promoter-specific regions across the genome and that MMA(III)-induced upregulation of H3K18ac led to an altered binding pattern in a large number of genes that was most significant during the critical window for MMA(III)-induced UROtsa cells' malignant transformation. Some genes identified as having a differential binding pattern with H3K18ac, acted as upstream regulators of critical gene networks with known functions in tumor development and progression. The altered H3K18ac binding patterns not only led to changes in expression of these directly affected upstream regulators but also resulted in gene-expression changes in their regulated networks. Collectively, our data suggest that MMA(III)-induced alteration of histone acetylation patterns in UROtsa cells led to a time-and malignant stage-dependent aberrant gene-expression pattern, and that some gene regulatory networks were altered in accordance with their roles in carcinogenesis, probably contributing to MMA(III)-induced urothelial cell malignant transformation and carcinogenesis.
机译：我们以前的研究表明，在恶性转化过程中，慢性暴露于低剂量的单甲基甲酸（MMA（III））导致尿路皮细胞（尿尿细胞）中的全球组蛋白乙酰化失调。为了揭示改变的组蛋白乙酰化模式和异常基因表达之间的关系，更具体地，这些改变的致癌相关性，我们在基因组和产生的全球中进行了组蛋白3赖氨酸18乙酰化（H3K18Ac）的结合模式的时间过程分析来自该尿素细胞恶性转化模型的基因表达谱。我们表明，H3K18AC是MMA（III）曝光后最明显上调的组蛋白乙酰化位点之一，在基因组上富集，并且MMA（III） - 诱导H3K18AC的上调导致改变的结合图案在MMA（III）的关键窗口中，大量基因最重要的是MMA（III） - 诱导的尿尿剂细胞的恶性转化。一些鉴定为具有H3K18Ac的差异结合模式的一些基因作用于临界基因网络的上游调节因子，具有肿瘤发育和进展的已知功能。改变的H3K18AC结合模式不仅导致了这些直接受影响的上游调节因子的表达的变化，而且导致其受监管网络中的基因表达变化。统称，我们的数据表明，MMA（III） - 诱导尿布细胞中组蛋白乙酰化模式的改变导致时间和恶性阶段依赖性异常的异常基因表达模式，并且一些基因监管网络根据其作用而改变致癌物质，可能导致MMA（III）诱导尿路上皮细胞恶性转化和致癌作用。

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  • 来源
    《Carcinogenesis》 |2017年第4期|共13页
  • 作者

    Zhu Jinqiu; Wang Jie; Chen Xushen; Tsompana Maria; Gaile Daniel; Buck Michael; Ren Xuefeng;

  • 作者单位

    SUNY Buffalo Dept Epidemiol &

    Environm Hlth Buffalo NY 14260 USA;

    SUNY Buffalo Dept Biochem Buffalo NY USA;

    SUNY Buffalo Dept Epidemiol &

    Environm Hlth Buffalo NY 14260 USA;

    SUNY Buffalo Dept Biochem Buffalo NY USA;

    SUNY Buffalo Dept Biostat Buffalo NY USA;

    SUNY Buffalo Dept Biochem Buffalo NY USA;

    SUNY Buffalo Dept Epidemiol &

    Environm Hlth Buffalo NY 14260 USA;

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  • 正文语种 eng
  • 中图分类 肿瘤学;
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