Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin

被引：101
作者：
Bauer, Daniel E. [1 ,2 ,3 ,4 ]
Orkin, Stuart H. [1 ,2 ,3 ,4 ,5 ]
机构：
[1] Boston Childrens Hosp, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Harvard Stem Cell Inst, Cambridge, MA 02138 USA
[5] Howard Hughes Med Inst, Boston, MA 02115 USA
来源：
CURRENT OPINION IN GENETICS & DEVELOPMENT | 2015年 / 33卷
关键词：
REGULATES HEMATOPOIETIC STEM; GENOME-WIDE ASSOCIATION; ZINC-FINGER PROTEIN; GLOBIN GENE; BETA-GLOBIN; HUMAN ERYTHROBLASTS; GAMMA-GLOBIN; EXPRESSION; ERYTHROPOIESIS; MICRODELETION;
D O I：
10.1016/j.gde.2015.08.001
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The major disorders of beta-globin, sickle cell disease and beta-thalassemia, may be ameliorated by expression of the fetal gene paralog gamma-globin. Uncertainty regarding the mechanisms repressing fetal hemoglobin in the adult stage has served as a puzzle of developmental gene regulation as well as a barrier to rational therapeutic design. Recent genome-wide association studies implicated the zinc-finger transcriptional repressor BCL11A in fetal hemoglobin regulation. Extensive genetic analyses have validated BCL11A as a potent repressor of fetal hemoglobin level. Studies of BCL11A exemplify how contextual gene regulation may often be the substrate for trait-associated common genetic variation. These discoveries have suggested novel rational approaches for the beta-hemoglobin disorders including therapeutic genome editing.
引用
收藏
页码：62 / 70
页数：9
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