DNA methylation profiling of transcription factor genes in normal lymphocyte development and lymphomas
DNA methylation profiling of transcription factor genes in normal lymphocyte development and lymphomas
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DOI：
10.1016/j.biocel.2007.02.006
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Eckhardt, Florian
中科院分区：
文献类型：
--
作者：
Ivascu, Claudia;Wasserkort, Reinhold;Eckhardt, Florian
转录因子在造血过程中起着至关重要的作用，通过协调谱系承诺和决定细胞命运。尽管转录因子表达的严格调控似乎是必不可少的，但对转录因子基因调控所涉及的表观遗传机制知之甚少。我们分析了造血级联、淋巴瘤细胞系和弥漫性大b细胞和t细胞非霍奇金淋巴瘤患者淋巴结活检的原代细胞中13个关键转录因子基因的DNA甲基化谱。几种转录因子基因（SPI1, GATA3, TCF-7, Erv5， c-maf和TBX21）在造血级联的特定细胞系和阶段中存在差异甲基化。对于一些基因，如SPI1、EtV5和Eomes，我们发现5'非翻译区的甲基化与相关基因的表达呈负相关，这表明这些基因受DNA甲基化调节。差异甲基化并不局限于健康的造血级联细胞，正如我们在弥漫性大b细胞淋巴瘤中观察到的c-maf、TCF7、Eomes和SPI1的异常甲基化。我们的研究结果表明，转录因子基因的表观遗传重塑是造血发育过程中一个常见的机制。在弥漫性大b细胞淋巴瘤中经常观察到转录因子基因的异常甲基化，并可能在肿瘤发生过程中发挥功能作用。(c) 2007 Elsevier Ltd.版权所有。
Transcription factors play a crucial role during hematopoiesis by orchestrating lineage commitment and determining cellular fate. Although tight regulation of transcription factor expression appears to be essential, little is known about the epigenetic mechanisms involved in transcription factor gene regulation. We have analyzed DNA methylation profiles of 13 key transcription factor genes in primary cells of the hematopoietic cascade, lymphoma cell lines and lymph node biopsies of diffuse large B-cell- and T-cellnon-Hodgkin lymphoma patients. Several of the transcription factor genes (SPI1, GATA3, TCF-7, Erv5, c-maf and TBX21) are differentially methylated in specific cell lineages and stages of the hematopoietic cascade. For some genes, such as SPI1, EtV5 and Eomes, we found an inverse correlation between the methylation of the 5' untranslated region and expression of the associated gene suggesting that these genes are regulated by DNA methylation. Differential methylation is not limited to cells of the healthy hematopoietic cascade, as we observed aberrant methylation of c-maf, TCF7, Eomes and SPI1 in diffuse large B-cell lymphomas. Our results suggest that epigenetic remodelling of transcription factor genes is a frequent mechanism during hematopoietic development. Aberrant methylation of transcription factor genes is frequently observed in diffuse large B-cell lymphomas and might have a functional role during tumorigenesis. (c) 2007 Elsevier Ltd. All rights reserved.