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首页> 外文期刊>PLoS Genetics >Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis
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Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis

机译：Menin结合的全基因组分析提供了对MEN1肿瘤发生的见解。

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Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin-targeted genes several hundred-fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients.
机译：I型多发性内分泌肿瘤（MEN1）是一种家族性癌症综合征，主要特征是多发性内分泌腺瘤。 MEN1的基因编码一种普遍表达的肿瘤抑制蛋白，称为Menin。最近显示，Menin与三胸家庭组蛋白甲基转移酶复合物的多个成分相互作用，包括ASH2，Rbbp5，WDR5和白血病原癌蛋白MLL。为了阐明menin作为肿瘤抑制因子的作用并深入了解MEN1中内分泌特异性肿瘤表型，我们使用以下方法将menin，MLL1和Rbbp5的基因组结合位点定位于HeLa S3，HepG2和胰腺胰岛细胞中约20,000个启动子染色质免疫沉淀与微阵列分析相结合的策略。我们发现，menin，MLL1和Rbbp5定位于数千种人类基因的启动子，但并不总是结合在一起。这些数据表明，menin可作为转录的一般调节子。我们还发现，因子占用通常与高基因表达相关，但menin的丧失不会导致大多数转录本水平发生重大变化。一个例外是发育程序化的转录因子HLXB9，它在缺乏menin的情况下在胰岛中过表达。我们的发现将针对menin的基因的领域扩大了数百倍，超出了先前描述的范围，并为在MEN1患者中观察到的内分泌肿瘤偏倚提供了潜在的见解。

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