Yagi M, Gelinas R, Elder J T, Peretz M, Papayannopoulou T, Stamatoyannopoulos G, Groudine M
Mol Cell Biol. 1986 Apr;6(4):1108-16. doi: 10.1128/mcb.6.4.1108-1116.1986.
The human alpha-like globins undergo a switch from the embryonic zeta-chain to the alpha-chain early in human development, at approximately the same time as the beta-like globins switch from the embryonic epsilon-to the fetal gamma-chains. We investigated the chromatin structure of the human alpha-globin gene cluster in fetal and adult erythroid cells. Our results indicate that DNase I-hypersensitive sites exist at the 5' ends of the alpha 1- and alpha 2-globin genes as well as at several other sites in the cluster in all erythroid cells examined. In addition, early and late fetal liver erythroid cells and adult bone marrow cells contain hypersensitive sites at the 5' end of the zeta gene, and in a purified population of 130-day-old fetal erythroid cells, the entire zeta-to alpha-globin region is sensitive to DNase I digestion. The presence of features of active chromatin in the zeta-globin region in fetal liver and adult bone marrow cells led us to investigate the transcription of zeta in these cells. By nuclear runoff transcription studies, we showed that initiated polymerases are present on the zeta-globin gene in these normal erythroid cells. Immunofluorescence with anti-zeta-globin antibodies also showed that late fetal liver cells contain zeta-globin. These findings demonstrate that expression of the embryonic zeta-globin continues at a low level in normal cells beyond the embryonic to fetal globin switch.
人类α样珠蛋白在人类发育早期会从胚胎型ζ链转换为α链，大约与β样珠蛋白从胚胎型ε链转换为胎儿型γ链的时间相同。我们研究了胎儿和成人红系细胞中人类α珠蛋白基因簇的染色质结构。我们的结果表明，在所检测的所有红系细胞中，α1和α2珠蛋白基因的5′端以及基因簇中的其他几个位点存在DNase I超敏位点。此外，胎儿肝脏早期和晚期红系细胞以及成人骨髓细胞在ζ基因的5′端含有超敏位点，在一群纯化的130日龄胎儿红系细胞中，整个ζ到α珠蛋白区域对DNase I消化敏感。胎儿肝脏和成人骨髓细胞中ζ珠蛋白区域存在活性染色质特征，这促使我们研究这些细胞中ζ的转录情况。通过核转录物延伸转录研究，我们表明在这些正常红系细胞的ζ珠蛋白基因上存在起始聚合酶。用抗ζ珠蛋白抗体进行免疫荧光检测也表明，胎儿肝脏晚期细胞含有ζ珠蛋白。这些发现表明，在正常细胞中，从胚胎到胎儿的珠蛋白转换之后，胚胎型ζ珠蛋白仍以低水平持续表达。
