Kulozik A E, Bail S, Bellan-Koch A, Bartram C R, Kohne E, Kleihauer E
Department of Pediatrics II, University of Ulm, Germany.
J Clin Invest. 1991 Jun;87(6):2142-6. doi: 10.1172/JCI115246.
In addition to local sequence elements the regulation of the high-level, development- and tissue-specific expression of the human beta globin gene cluster appears to require distant regulatory sequences which have been termed locus control region. In the chromatin of erythroid cells the locus control region is characterized by four DNaseI hypersensitive sites that are located 6-18 kb 5' of the epsilon globin gene. The definition of the sequences minimally required for locus control region activity is likely to further the understanding of its physiology and will be of interest for the development of somatic gene therapy strategies of the hemoglobinopathies. We present here the analysis of a family with a 3,030-bp deletion of sequences upstream of the epsilon globin gene including the most 3' locus control region element and cosegregating beta(0) thalassemia. The deletion is linked in cis to a structurally and functionally normal beta globin gene. The proximal element of the locus control region does not therefore appear to be necessary for beta globin gene activity in vivo.
除了局部序列元件外，人类β珠蛋白基因簇的高水平、发育和组织特异性表达的调控似乎还需要远距离调控序列，这些序列被称为基因座控制区。在红系细胞的染色质中，基因座控制区的特征是四个脱氧核糖核酸酶I超敏位点，它们位于ε珠蛋白基因5'端6 - 18 kb处。确定基因座控制区活性所需的最小序列定义可能会进一步加深对其生理学的理解，并且对于血红蛋白病的体细胞基因治疗策略的开发具有重要意义。我们在此展示了一个家族的分析结果，该家族的ε珠蛋白基因上游序列发生了3030 bp的缺失，包括最3'端的基因座控制区元件，并伴有β⁰地中海贫血。该缺失与结构和功能正常的β珠蛋白基因顺式连接。因此，基因座控制区的近端元件在体内对于β珠蛋白基因的活性似乎并非必需。
