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

被引：106

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

页码：62 / 70

页数：9

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