Foley K P, Pruzina S, Winick J D, Engel J D, Grosveld F, Fraser P
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7252-6. doi: 10.1073/pnas.91.15.7252.
In transiently transfected chicken erythroid cells, beta-like globin gene switching is mediated through differential activation of the cis-linked embryonic epsilon- and adult beta-globin genes by a shared enhancer. Two underlying mechanisms have been proposed: (i) tissue- and stage-specific factors activate the beta-globin promoter in adult erythroid cells (autonomous regulation); and (ii) the epsilon-globin promoter, although transcriptionally competent in both embryonic and adult cells, is suppressed at the adult stage through competition with the beta-globin promoter for interaction with the enhancer (competitive regulation). Analyses of transgenic mice carrying the chicken beta/epsilon-globin locus demonstrated that both genes depended on the enhancer for erythroid expression, but only the epsilon-globin gene exhibited developmentally appropriate transcription at levels comparable to the endogenous mouse globin genes. Surprisingly, the chicken epsilon-globin gene also appeared to be autonomously regulated, as has been observed for human embryonic and fetal beta-like globin genes in transgenic mice. These results suggest that the chicken beta/epsilon-globin enhancer possesses either embryonic stage or epsilon-globin gene specificity when incorporated into the murine germ line.
在瞬时转染的鸡红细胞中，β样珠蛋白基因转换是通过一个共享增强子对顺式连接的胚胎ε珠蛋白基因和成人β珠蛋白基因的差异激活来介导的。已经提出了两种潜在机制：（i）组织和阶段特异性因子在成人红细胞中激活β珠蛋白启动子（自主调节）；（ii）ε珠蛋白启动子虽然在胚胎细胞和成人细胞中都具有转录活性，但在成人阶段通过与β珠蛋白启动子竞争与增强子的相互作用而受到抑制（竞争调节）。对携带鸡β/ε珠蛋白基因座的转基因小鼠的分析表明，这两个基因的红细胞表达都依赖于增强子，但只有ε珠蛋白基因在与内源性小鼠珠蛋白基因相当的水平上表现出发育上适当的转录。令人惊讶的是，鸡ε珠蛋白基因似乎也受到自主调节，就像在转基因小鼠中观察到的人类胚胎和胎儿β样珠蛋白基因一样。这些结果表明，当整合到小鼠种系中时，鸡β/ε珠蛋白增强子具有胚胎阶段或ε珠蛋白基因特异性。
