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首页> 外文期刊>Genomics >The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5.
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The KCNQ1OT1 promoter, a key regulator of genomic imprinting in human chromosome 11p15.5.

机译：KCNQ1OT1启动子，人类染色体11p15.5中基因组印迹的关键调节子。

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摘要

The human 11p15.5 region contains several maternally and paternally imprinted genes. Dysregulation of imprinting of some of these genes occurs in the Beckwith-Wiedemann syndrome and several tumors. Imprinting in this region is controlled by two imprinting control regions (ICR). ICR1 acts as an insulator that regulates the reciprocal imprinting of the IGF2 and H19 genes. A differentially methylated region in ICR2 regulates the expression of a long transcript called KCNQ1OT1. This paternally expressed transcript negatively regulates several paternally imprinted genes around ICR2. Biallelic expression of the KCNQ1OT1 transcript is the primary molecular defect in over 50% of cases of Beckwith-Wiedemann syndrome. To understand the role of KCNQ1OT1 in regulating ICR2 we characterized its promoter. The critical promoter is approximately 300 bp and it is surrounded by inhibitory elements within the CpG island. The promoter activity is strongly inhibited by cytosine methylation in keeping with the finding that the inactive maternal promoter is methylated in vivo. We have identified the transcription start sites and four CCAAT boxes upstream of the 5'-most start site. Mutation of the CCAAT boxes produced impairment of promoter activity. Transfection and gel mobility shift experiments suggest that binding of the factor NF-Y to the CCAAT boxes is important for promoter activity.
机译：人的11p15.5区域包含几个母体和父体印迹的基因。 Beckwith-Wiedemann综合征和一些肿瘤中某些基因的印记失调。该区域中的压印由两个压印控制区域（ICR）控制。 ICR1充当调节IGF2和H19基因相互印记的绝缘子。 ICR2中的一个差异甲基化区域调节一个称为KCNQ1OT1的长转录子的表达。父本表达的转录产物负调控ICR2周围的几个父本印迹基因。在50％以上的Beckwith-Wiedemann综合征病例中，KCNQ1OT1转录本的双等位基因表达是主要的分子缺陷。为了了解KCNQ1OT1在调节ICR2中的作用，我们对其启动子进行了表征。关键启动子约为300 bp，被CpG岛内的抑制性元件包围。与无活性的母体启动子在体内甲基化的发现一致，胞嘧啶甲基化强烈抑制了启动子活性。我们已经确定了转录起始位点和最靠近5'起始位点上游的四个CCAAT框。 CCAAT盒的突变导致启动子活性受损。转染和凝胶迁移率迁移实验表明，因子NF-Y与CCAAT盒的结合对于启动子活性很重要。

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