Stamatoyannopoulos George
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA.
Exp Hematol. 2005 Mar;33(3):259-71. doi: 10.1016/j.exphem.2004.11.007.
Extensive studies during the last 30 years have led to considerable understanding of cellular and molecular control of hemoglobin switching. Cell biology studies in the 1970s defined the control of globin genes during erythroid differentiation and led to development of therapies for sickle cell disease. Molecular investigations of the last 20 years have delineated the two basic mechanisms that control globin gene activity during development--autonomous silencing and gene competition. Studies of hemoglobin switching have provided major insights on the control of gene loci by remote regulatory elements. Research in this field has an impact on understanding regulatory mechanisms in general and is of particular importance for eventual development of molecular cures for sickle cell disease and beta thalassemia.
在过去30年里进行的广泛研究，使人们对血红蛋白转换的细胞和分子控制有了相当深入的了解。20世纪70年代的细胞生物学研究确定了红系分化过程中珠蛋白基因的控制机制，并促成了镰状细胞病治疗方法的发展。过去20年的分子研究已经阐明了在发育过程中控制珠蛋白基因活性的两种基本机制——自主沉默和基因竞争。对血红蛋白转换的研究为远程调控元件对基因位点的控制提供了重要见解。该领域的研究总体上有助于理解调控机制，对于最终开发镰状细胞病和β地中海贫血的分子疗法尤为重要。
