Analysis for transcriptional regulation of the BCL6 gene

BCL6基因转录调控分析

• 批准号: 09671098
• 负责人: MIKI Tohru
• 金额: $ 1.92万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671098/
• 关键词: BCL6; malignant; Transcription factor; Gene expression; Science; 染色体転座; 胚中心

Rearrangements of the BCL6 gene have been frequently found in human B-cell lymphomas, as a result of reciprocal chromosomal translocation involving band 3q27. Chromosomal breaks preferentially occur within a 3-kb region containing the first exon and intron of thh BCL6 gene. Recent reports revealed that internal deletions or point mutations within this limited region are also common in B-cell lymphomas. These observations suggest that the structural alteration of the first exon-intron boundary region of the BCL6 gene, a putative regulatory region, may be crucial event in the development of B-cell lymphomas. To further understand the mechanism of the deregulated expression of BCL6 in lymphomas, we investigated the physiological function of this region in transcriptional regulation of the BCL6 gene.Through luciferase reporter assay using B-cell line Raji, we have identified two regions that negatively regulate BCL6 expression. One region designated as ES located within the first exon betw … More een nucleotides +472 and +543, and the other region designated as IS between +783 and +918 of the first intron. Consensus nucleotide sequence for a binding of BCL6 protein itself was found within the ES region. Subsequent electrophoretic mobility shift assay revealed an actual binding of BCL6 to the ES region. Co-transfection experiment using a BCL6 expression vector showed that transcription of the BCL6 gene was partly regulated by a negative feedback of the BCL6 gene product.Another negative regulatory region IS has been shown to have a silencer activity. The IS region is entirely included in the regions commonly deleted in B-cell lymphomas as well as in the parts where somatic hypermutations are found in both normal and neoplastic B-cells. Electrophoretic mobility shift assay showed that the nuclear proteins that specifically bind to this intronic silencer element are expressed in several hematopoietic cell lines.Taken together, the identified regions of the BCL6 gene contain negative regulatory elements and the structural alterations of these regions have potential roles in the deregulated expression of the BCL6 gene in B-cell lymphomas. Less

在人类B细胞淋巴瘤中经常发现BCL 6基因重排，这是由于涉及带3q 27的相互染色体易位的结果。染色体断裂优先发生在含BCL 6基因第一个外显子和内含子的3 kb区域内。最近的报告显示，在这个有限的区域内的内部缺失或点突变在B细胞淋巴瘤中也很常见。这些观察结果表明，BCL 6基因的第一个外显子-内含子边界区的结构改变，一个假定的调节区，可能是B细胞淋巴瘤的发展中的关键事件。为了进一步了解BCL 6在淋巴瘤中表达失调的机制，我们研究了该区域在BCL 6基因转录调控中的生理功能。通过使用B细胞系Raji的荧光素酶报告基因分析，我们已经确定了两个负调控BCL 6表达的区域。一个区域命名为ES，位于第一个外显子之间， ...更多信息 第一个内含子的+472和+543之间的一个核苷酸区域，以及第一个内含子的+783和+918之间的另一个区域被指定为IS。在ES区域内发现了BCL 6蛋白本身结合的共有核苷酸序列。随后的电泳迁移率变动分析显示BCL 6与ES区域的实际结合。共转染实验表明，BCL 6基因的转录部分受BCL 6基因产物的负反馈调控，另一个负调控区IS具有沉默活性。IS区域完全包括在B细胞淋巴瘤中通常缺失的区域中以及在正常和肿瘤性B细胞中发现体细胞超突变的部分中。电泳迁移率变动分析表明，与该内含子沉默元件特异性结合的核蛋白在几种造血细胞系中均有表达，综合考虑，BCL 6基因的已鉴定区域含有负调控元件，这些区域的结构改变可能在B细胞淋巴瘤中BCL 6基因表达失调中起作用。少

项目成果

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Ohshima,A 等人：“54 名非哈尔津淋巴瘤患者中影响 3q27 的 BCL6 基因重排和染色体畸变”白血病淋巴瘤。

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