Identification of novel Bach2 transcripts and protein isoforms through tagging analysis of retroviral integrations in B-cell lymphomas
Identification of novel Bach2 transcripts and protein isoforms through tagging analysis of retroviral integrations in B-cell lymphomas
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DOI：
10.1186/1471-2199-10-2
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发表时间：
2009-01-21
影响因子：
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通讯作者：
Pedersen, Finn Skou
中科院分区：
文献类型：
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作者：
Liu, Jinghua;Sorensen, Annette Balle;Pedersen, Finn Skou
背景：Bach 2基因在B细胞中作为转录抑制因子发挥作用，仅在浆细胞阶段之前表现出高表达水平。几条证据表明Bach 2是B细胞特异性肿瘤抑制因子。我们在这里解决的插入突变和表达的Bach2的模式是一个小鼠逆转录病毒模型的B细胞淋巴瘤induction.Results：我们报告说，Bach2基因是一个目标，在小鼠白血病病毒诱导的B细胞淋巴瘤的前病毒整合。在内含子2内鉴定了另一种Bach 2启动子，并且该启动子在携带前病毒整合的肿瘤之一中被激活。替代启动子在正常和肿瘤组织中均具有活性，并且两种Bach 2启动子的组织特异性相似。三个不同的替代使用巴赫2末端外显子被确定为位于内含子4。包含这些外显子导致产生具有开放阅读框的Bach2 mRNA，其缺乏正常Bach2蛋白中存在的bZIP DNA结合结构域，但保留部分BTB蛋白二聚化结构域。结论：我们已经确定了一个替代的启动子和新的蛋白质亚型的Bach 2。我们的数据表明，激活的替代启动子前病毒整合作为一个可能的机制，上调Bach2基因在B细胞淋巴瘤发生的潜在作用。新的Bach2转录本和蛋白质亚型的发现将有助于更好地了解Bach2基因的正常和病理生理调节。
Background: The Bach2 gene functions as a transcriptional repressor in B-cells, showing high expression level only before the plasma cell stage. Several lines of evidence indicate that Bach2 is a B-cell specific tumor suppressor. We here address patterns of insertional mutagenesis and expression of Bach2 is a murine retroviral model of B-cell lymphoma induction.Results: We report that the Bach2 gene is a target of proviral integrations in B-cell lymphomas induced by murine leukemia virus. An alternative Bach2 promoter was identified within intron 2 and this promoter was activated in one of the tumors harboring proviral integration. The alternative promoter was active in both normal and tumor tissue and the tissue specificity of the two Bach2 promoters was similar. Three different alternatively used Bach2 terminal exons were identified to be located in intron 4. The inclusion of these exons resulted in the generation of Bach2 mRNA with open reading frames lacking the bZIP DNA binding domain present in the normal Bach2 protein, but retaining a partial BTB protein dimerization domain. Such Bach2 protein was excluded from the cell nucleus.Conclusion: We have identified an alternative promoter and new protein isoforms of Bach2. Our data imply that activation of an alternative promoter by proviral integration serves as a possible mechanism of up-regulation of the Bach2 gene with a potential role in B-cell lymphomagenesis. The finding of novel Bach2 transcripts and protein isoforms will facilitate a better insight into the normal and pathophysiological regulation of the Bach2 gene.