Inferring a role for methylation of intergenic DNA in the regulation of genes aberrantly expressed in precursor B-cell acute lymphoblastic leukemia.
Inferring a role for methylation of intergenic DNA in the regulation of genes aberrantly expressed in precursor B-cell acute lymphoblastic leukemia.
复制标题
DOI：
10.1080/10428194.2016.1272683
复制
发表时间：
2017-09
影响因子：
2.6
通讯作者：
Taylor KH
中科院分区：
文献类型：
--
作者：
Almamun M;Kholod O;Stuckel AJ;Levinson BT;Johnson NT;Arthur GL;Davis JW;Taylor KH
对前B组ALL的发病机制缺乏完整的了解。在这项研究中，我们结合DNA甲基化数据和基因表达数据来阐明基因间异常甲基化对前B-ALL基因表达的影响。我们发现了一组差异甲基化的基因间基因座，它们与前B-ALL患者的基因表达改变有关。值得注意的是，其中84%的区域还与转录因子结合，已知转录因子在淋巴母细胞系中的分化和B细胞发育中发挥作用。此外，在前B-ALL患者中观察到ERNA转录本的整体下调，这些转录本与与B细胞迁移、增殖和凋亡相关的可能的靶基因的下调有关。新的假定调节区的识别突出了基因间DNA序列的重要性，并可能有助于识别治疗前B-ALL的新的治疗靶点。
A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors known to play roles in differentiation and B-cell development in a lymphoblastoid cell line. Further, an overall down-regulation of eRNA transcripts was observed in pre-B ALL patients and these transcripts were associated with the down-regulation of putative target genes involved in B-cell migration, proliferation and apoptosis. The identification of novel putative regulatory regions highlights the significance of intergenic DNA sequences and may contribute to the identification of new therapeutic targets for the treatment of pre-B ALL.