Smith R D, Yu J
J Biol Chem. 1984 Apr 10;259(7):4609-15.
Adult beta-globin gene chromatin in murine erythroleukemia (MEL) cells acquired increased sensitivity to both micrococcal nuclease and DNase I during hexamethylenebisacetamide-induced erythoid differentiation. The DNase I hypersensitivity of the globin genes accompanied their actual transcription and was strongly correlated with commitment events. On the other hand, the rate of micrococcal nuclease digestion was closely related to the rate of globin gene transcription. Two distinct DNase I hypersensitive sites were found on the 5' side of the beta-major globin gene in HMBA-induced cells. One site was located near the 5' side of the beta-major globin gene and the second site was located approximately 3 kilobases upstream of the beta-major cap site. Following the commitment of MEL cells to differentiate, DNase I sensitivity was stably inherited in the absence of inducer. In contrast to HMBA, another inducer, hemin, known to cause the accumulation of globin-specific mRNA in MEL cells by a post-transcriptional mechanism, did not elicit alterations of beta-globin gene chromatin. The addition of dexamethasone, a hormone known to inhibit MEL cell commitment, blocked the formation of general and site-specific nuclease sensitivity of beta-globin gene chromatin prior to but not after cell commitment.
在六亚甲基双乙酰胺诱导的红系分化过程中，鼠类红白血病（MEL）细胞中的成人β-珠蛋白基因染色质对微球菌核酸酶和DNase I的敏感性增加。珠蛋白基因的DNase I超敏感性伴随着它们的实际转录，并且与定向事件密切相关。另一方面，微球菌核酸酶的消化速率与珠蛋白基因的转录速率密切相关。在HMBA诱导的细胞中，在β-珠蛋白主基因的5'侧发现了两个不同的DNase I超敏感位点。一个位点位于β-珠蛋白主基因的5'侧附近，第二个位点位于β-珠蛋白主基因帽位点上游约3千碱基处。在MEL细胞定向分化后，在没有诱导剂的情况下，DNase I敏感性稳定遗传。与HMBA相反，另一种诱导剂血红素，已知通过转录后机制导致MEL细胞中珠蛋白特异性mRNA的积累，但不会引起β-珠蛋白基因染色质的改变。地塞米松是一种已知可抑制MEL细胞定向分化的激素，在细胞定向之前添加地塞米松会阻断β-珠蛋白基因染色质的一般和位点特异性核酸酶敏感性的形成，但在细胞定向之后则不会。
