Construction and analysis of cells lacking the HMGA gene family
Construction and analysis of cells lacking the HMGA gene family
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DOI：
10.1093/nar/gkg684
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发表时间：
2003-09-01
影响因子：
14.9
通讯作者：
Bushman, F
中科院分区：
文献类型：
--
作者：
Beitzel, B;Bushman, F
非组蛋白染色体蛋白的高迁移率族A（HMGA）家族由两个相关基因HMGA 1和HMGA 2编码。HMGA蛋白是一种结构性转录因子，已发现其调节大量基因的转录。它们也是人类肿瘤中最常见的失调基因，突出了在生长控制中的作用。还发现HMGA1和HMGA2在体外刺激逆转录病毒整合。在这项研究中，我们克隆了鸡HMGA 1，并使用鸡DT 40 B细胞淋巴瘤系产生缺乏HMGA 1，HMGA 2和两者组合的细胞。我们测试了这些细胞系对细胞生长、基因控制和逆转录病毒整合的影响。令人惊讶的是，我们发现HMGA基因家族在DT 40细胞中生长缓慢，并且在不存在HMGA 1或HMGA 2的情况下，逆转录病毒整合没有明显缺陷。我们还分析了大约4000个鸡基因的活性，但没有发现明显的变化。我们的结论是，HMGA蛋白并不严格需要生长控制或逆转录病毒整合在DT 40细胞，并可能是多余的与其他因素。
The high mobility group A (HMGA) family of non-histone chromosomal proteins is encoded by two related genes, HMGA1 and HMGA2. HMGA proteins are architectural transcription factors that have been found to regulate the transcription of a large number of genes. They are also some of the most commonly dysregulated genes in human neoplasias, highlighting a role in growth control. HMGA1 and HMGA2 have also been found to stimulate retroviral integration in vitro. In this study, we have cloned chicken HMGA1, and used the chicken DT40 B-cell lymphoma line to generate cells lacking HMGA1, HMGA2 and both in combination. We tested these lines for effects on cellular growth, gene control and retroviral integration. Surprisingly, we found that the HMGA gene family is dispensable for growth in DT40 cells, and that there is no apparent defect in retroviral integration in the absence of HMGA1 or HMGA2. We also analyzed the activity of approximately 4000 chicken genes, but found no significant changes. We conclude that HMGA proteins are not strictly required for growth control or retroviral integration in DT40 cells and may well be redundant with other factors.