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首页> 外文期刊>The FEBS journal >Overexpression of human histone methylase MLL 1 upon exposure to a food contaminant mycotoxin, deoxynivalenol
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Overexpression of human histone methylase MLL 1 upon exposure to a food contaminant mycotoxin, deoxynivalenol

机译：人组蛋白甲基化酶MLL 1在接触食物污染物霉菌毒素脱氧雪腐烯醇后过表达

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摘要

Mixed lineage leukemias (MLLs) are histone-methylating enzymes with critical roles in gene expression, epigenetics and cancer. Although MLLs are important gene regulators little is known about their own regulation. Herein, to understand the effects of toxic stress on MLL gene regulation, we treated human cells with a common food contaminant mycotoxin, deoxynivalenol (DON). Our results demonstrate that MLLs and Hox genes are overexpressed upon exposure to DON. Studies using specific inhibitors demonstrated that Src kinase families are involved in upstream events in DON-mediated upregulation of MLL1. Sequence analysis demonstrated that the MLL 1 promoter contains multiple Sp1-binding sites and importantly, the binding of Sp 1 is enriched in the MLL 1 promoter upon exposure to DON. Moreover, antisense-mediated knockdown of Sp 1 diminished DON-induced MLL 1 upregulation. These results demonstrated that MLL 1 gene expression is sensitive to toxic stress and Sp 1 plays crucial roles in the stress-induced upregulation of MLL1.
机译：混合谱系白血病（MLL）是组蛋白甲基化酶，在基因表达，表观遗传学和癌症中起关键作用。尽管MLL是重要的基因调节剂，但对其自身的调节知之甚少。本文中，为了了解毒性应激对MLL基因调控的影响，我们用常见的食物污染物霉菌毒素脱氧雪腐烯醇（DON）处理了人类细胞。我们的结果表明，MLL和Hox基因在暴露于DON后过表达。使用特定抑制剂的研究表明Src激酶家族参与DON介导的MLL1上调的上游事件。序列分析表明MLL 1启动子包含多个Sp1结合位点，重要的是，Sp 1的结合在暴露于DON后在MLL 1启动子中富集。而且，Sp 1的反义介导的敲低减少了DON诱导的MLL 1上调。这些结果表明，MLL 1基因表达对毒性应激敏感，Sp 1在应激诱导的MLL1上调中起关键作用。

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