血红蛋白转换的惊人发现：多功能转录因子BCL11A是胎儿血红蛋白的主要抑制因子。
Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin.
作者信息
Bauer Daniel E, Orkin Stuart H
机构信息
Boston Children's Hospital, Boston, MA 02115, United States; Dana-Farber Cancer Institute, Boston, MA 02115, United States; Harvard Medical School, Boston, MA 02115, United States; Harvard Stem Cell Institute, Cambridge, MA 02138, United States.
Boston Children's Hospital, Boston, MA 02115, United States; Dana-Farber Cancer Institute, Boston, MA 02115, United States; Harvard Medical School, Boston, MA 02115, United States; Harvard Stem Cell Institute, Cambridge, MA 02138, United States; Howard Hughes Medical Institute, Boston, MA 02115, United States.
出版信息
Curr Opin Genet Dev. 2015 Aug;33:62-70. doi: 10.1016/j.gde.2015.08.001. Epub 2015 Sep 14.
The major disorders of β-globin, sickle cell disease and β-thalassemia, may be ameliorated by expression of the fetal gene paralog γ-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 β-hemoglobin disorders including therapeutic genome editing.
β-珠蛋白的主要疾病，即镰状细胞病和β-地中海贫血，可能通过胎儿基因旁系同源物γ-珠蛋白的表达得到改善。关于在成年期抑制胎儿血红蛋白的机制的不确定性，一直是发育基因调控的一个谜题，也是合理治疗设计的一个障碍。最近的全基因组关联研究表明，锌指转录抑制因子BCL11A参与胎儿血红蛋白的调控。广泛的基因分析已证实BCL11A是胎儿血红蛋白水平的有效抑制因子。对BCL11A的研究例证了背景基因调控如何常常成为与性状相关的常见基因变异的基础。这些发现为β-血红蛋白疾病提出了新的合理方法，包括治疗性基因组编辑。
Zotero 插件