CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells
CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells
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DOI：
10.4137/grsb.s11879
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发表时间：
2013-01-01
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影响因子：
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通讯作者：
Willey, James C.
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作者：
Blomquist, Thomas M.;Brown, Ronald D.;Willey, James C.
正常人支气管上皮细胞(NBEC)中CCAAT/增强子结合蛋白γ(CEBPG)转录表达的个体间差异与肺癌的易感性有关。我们假设，这种个体间的变异部分是由CEBPG中顺式作用的遗传变异解释的。为了验证这一假设，我们测量了CEBPG的每个亲本拷贝的转录表达(即，等位基因特异性表达；ASE)。CEBPG rs2772A的ASE比C等位基因的细胞周期特异性变异高2.9倍(P<；0.001)。在20%的NBEC样本中，CEBPG rs2772 A等位基因的表达平均是rs2772 C等位基因的2.10倍。这些数据支持这样的假设，即与rs2772连锁不平衡的遗传变异通过RNA聚合酶II转录下游的反式作用影响CEBPG转录表达的调节，并证实顺式作用的遗传变异导致NBEC中CEBPG转录表达的个体间差异，这与肺癌风险的变化有关。
Inter-individual variation in CCAAT/enhancer binding protein gamma (CEBPG) transcript expression in normal human bronchial epithelial cells (NBEC) is associated with predisposition to lung cancer. We hypothesize that this inter-individual variation is in part explained by cis-acting genetic variation in CEBPG. To test this hypothesis we measured transcript expression derived from each parental copy of CEBPG (ie, allele-specific expression; ASE). There was a significant 2.9-fold higher cell cycle-specific variation in ASE of CEBPG rs2772 A compared to C allele (P < 0.001). In 20% of NBEC samples, CEBPG rs2772 A allele was expressed on average 2.10 fold greater than rs2772 C allele. These data support the hypothesis that genetic variation in linkage disequilibrium with rs2772 influences regulation of CEBPG transcript expression through a trans-effect downstream of RNA polymerase II transcription and confirm that cis-acting genetic variation contributes to inter-individual variation in CEBPG transcript expression in NBEC, which is associated with variation in lung cancer risk.