Genome-wide DNA methylation analysis in precursor B-cells.
Genome-wide DNA methylation analysis in precursor B-cells.
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DOI：
10.4161/15592294.2014.983379
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发表时间：
2014-12
期刊：
影响因子：
3.7
通讯作者：
Taylor KH
中科院分区：
文献类型：
--
作者：
Almamun M;Levinson BT;Gater ST;Schnabel RD;Arthur GL;Davis JW;Taylor KH
DNA甲基化负责调节基因表达和细胞分化，并在正常人类发育期间维持基因组稳定性。此外，它在造血的调节中起着重要作用。为了阐明B细胞发育过程中DNA甲基化的影响，使用甲基化CpG岛恢复测定法，然后进行下一代测序，测定了从人脐带血中分离的pro-B、pre-BI、pre-BII和幼稚B细胞的全基因组DNA甲基化状态。平均而言，在10次生物学重复中，每个前体B细胞亚群产生了1.82 - 2亿个序列。在从pro-B到pre-BI的转变过程中观察到甲基化的总体降低，而在pre-BI到pre-BII的转变或pre-BII到幼稚B细胞的转变中没有观察到差异甲基化。大多数甲基化区域位于基因间和内含子区域内，而不存在于CpG岛环境中。推定的新的增强子被确定在这些地区之间的pro-B和前BI细胞的差异甲基化。全基因组甲基化谱是可利用的，并且可用于更好地理解与前体B细胞相关的恶性肿瘤的发病机制中非典型DNA甲基化的参与。
DNA methylation is responsible for regulating gene expression and cellular differentiation and for maintaining genomic stability during normal human development. Furthermore, it plays a significant role in the regulation of hematopoiesis. In order to elucidate the influence of DNA methylation during B-cell development, genome-wide DNA methylation status of pro-B, pre-BI, pre-BII, and naïve-B-cells isolated from human umbilical cord blood was determined using the methylated CpG island recovery assay followed by next generation sequencing. On average, 182–200 million sequences were generated for each precursor B-cell subset in 10 biological replicates. An overall decrease in methylation was observed during the transition from pro-B to pre-BI, whereas no differential methylation was observed in the pre-BI to pre-BII transition or in the pre-BII to naïve B-cell transition. Most of the methylated regions were located within intergenic and intronic regions not present in a CpG island context. Putative novel enhancers were identified in these regions that were differentially methylated between pro-B and pre-BI cells. The genome-wide methylation profiles are publically available and may be used to gain a better understanding of the involvement of atypical DNA methylation in the pathogenesis of malignancies associated with precursor B-cells.