CEBPG Exhibits Allele-Specific Expression in Human Bronchial Epithelial Cells.

Gene regulation and systems biology Pub Date : 2013-07-04 Print Date: 2013-01-01 DOI:10.4137/GRSB.S11879
Thomas M Blomquist, Ronald D Brown, Erin L Crawford, Ivana de la Serna, Kandace Williams, Youngsook Yoon, Dawn-Alita Hernandez, James C Willey
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引用次数: 11

Abstract

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.

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CEBPG在人支气管上皮细胞中表现出等位基因特异性表达。
正常人支气管上皮细胞(NBEC) CCAAT/增强子结合蛋白γ (CEBPG)转录物表达的个体间变异与肺癌易感性相关。我们假设CEBPG的顺式作用遗传变异部分解释了这种个体间变异。为了验证这一假设,我们测量了来自每个CEBPG亲本拷贝的转录本表达(即等位基因特异性表达;日月光半导体)。CEBPG rs2772a基因的ASE细胞周期特异性变异比C基因高2.9倍(P < 0.001)。在20%的NBEC样本中,CEBPG rs2772 A等位基因的平均表达量是rs2772 C等位基因的2.10倍。这些数据支持了与rs2772连锁不平衡的遗传变异通过RNA聚合酶II转录下游的反式效应影响CEBPG转录物表达调控的假设,并证实了顺式作用的遗传变异导致了NBEC中CEBPG转录物表达的个体间差异,而这种差异与肺癌风险的变化有关。
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