缺乏HMGA基因家族的细胞的构建与分析。
Construction and analysis of cells lacking the HMGA gene family.
作者信息
Beitzel Brett, Bushman Frederic
机构信息
Infectious Disease Laboratory, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Nucleic Acids Res. 2003 Sep 1;31(17):5025-32. doi: 10.1093/nar/gkg684.
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.
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HMGA1和HMGA2编码。HMGA蛋白是结构转录因子，已发现其可调节大量基因的转录。它们也是人类肿瘤中一些最常失调的基因，突显了其在生长控制中的作用。还发现HMGA1和HMGA2在体外可刺激逆转录病毒整合。在本研究中，我们克隆了鸡HMGA1，并利用鸡DT40 B细胞淋巴瘤系生成了缺乏HMGA1、HMGA2以及两者组合缺失的细胞。我们测试了这些细胞系对细胞生长、基因调控和逆转录病毒整合的影响。令人惊讶的是，我们发现HMGA基因家族对于DT40细胞的生长并非必需，并且在缺乏HMGA1或HMGA2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，但未发现显著变化。我们得出结论，HMGA蛋白对于DT40细胞的生长控制或逆转录病毒整合并非严格必需，很可能与其他因子功能冗余。
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