Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation
Allele-specific gene expression patterns in primary leukemic cells reveal regulation of gene expression by CpG site methylation
复制标题
DOI：
10.1101/gr.083931.108
复制
发表时间：
2009-01-01
期刊：
影响因子：
7
通讯作者：
Syvanen, Ann-Christine
中科院分区：
文献类型：
--
作者：
Milani, Lili;Lundmark, Anders;Syvanen, Ann-Christine
为了确定急性淋巴细胞白血病（ALL）中受顺式作用功能元件调控的基因，我们通过对197例ALL患儿骨髓和血液样本中RNA和DNA的全基因组单核苷酸多态性进行基因分型，确定了2529个基因的等位基因特异性表达（ASE）水平。使用可重复的定量基因分型方法和严格的ASE评分标准，我们发现16%的分析基因在多个ALL细胞样本中显示ASE。对于大多数基因，ASE的水平在样本之间变化很大，从一个等位基因的1.4倍过表达到表观单等位基因表达。对于表现出ASE的基因，55%显示双向ASE，其中两个SNP等位基因中的任一个发生过表达。对于双向ASE，我们还观察到总体较高的ASE水平，并与这些位点的甲基化水平相关。我们的研究结果表明，CpG位点甲基化是调节ALL细胞基因表达的因素之一。
To identify genes that are regulated by cis-acting functional elements in acute lymphoblastic leukemia (ALL) we determined the allele-specific expression (ASE) levels of 2529 genes by genotyping a genome-wide panel of single nucleotide polymorphisms in RNA and DNA from bone marrow and blood samples of 197 children with ALL. Using a reproducible, quantitative genotyping method and stringent criteria for scoring ASE, we found that 16% of the analyzed genes display ASE in multiple ALL cell samples. For most of the genes, the level of ASE varied largely between the samples, from 1.4-fold overexpression of one allele to apparent monoallelic expression. For genes exhibiting ASE, 55% displayed bidirectional ASE in which overexpression of either of the two SNP alleles occurred. For bidirectional ASE we also observed overall higher levels of ASE and correlation with the methylation level of these sites. Our results demonstrate that CpG site methylation is one of the factors that regulates gene expression in ALL cells.