C/EBPγ在转基因小鼠中的红系过表达影响γ珠蛋白表达和胎肝红细胞生成。
Erythroid overexpression of C/EBPgamma in transgenic mice affects gamma-globin expression and fetal liver erythropoiesis.
作者信息
Zafarana G, Rottier R, Grosveld F, Philipsen S
机构信息
Erasmus University Rotterdam, MGC-Department of Cell Biology, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
出版信息
EMBO J. 2000 Nov 1;19(21):5856-63. doi: 10.1093/emboj/19.21.5856.
Abstract
The CCAAT boxes of the beta-like globin genes interact with three proteins: NF-Y, GATA-1 and NFE-6. We demonstrate that NFE-6 contains C/EBPgamma, and address its role in globin gene regulation by erythroid overexpression of C/EBPgamma, and a dominant-negative form C/EBPgammaDeltaB, in mice. Elevated levels of C/EBPgamma, but not C/EBPgammaDeltaB, increase expression of the (fetal) gamma-globin relative to the (adult) beta-globin gene. Interestingly, fetal liver erythropoiesis is ablated when the C/EBPgamma and C/EBPgammaDeltaB levels are further increased in homozygous transgenics. We suggest that targeted expression of dominant-negative leucine zipper proteins is a generally applicable approach to ablate specific tissues in mice.
摘要
类β珠蛋白基因的CCAAT框与三种蛋白质相互作用：核因子Y（NF-Y）、GATA-1和NFE-6。我们证明NFE-6包含C/EBPγ，并通过在小鼠中红系过表达C/EBPγ和显性负性形式的C/EBPγΔB来探讨其在珠蛋白基因调控中的作用。相对于（成人）β珠蛋白基因，C/EBPγ水平升高，但C/EBPγΔB水平未升高，会增加（胎儿）γ珠蛋白的表达。有趣的是，在纯合转基因小鼠中，当C/EBPγ和C/EBPγΔB水平进一步升高时，胎儿肝脏红细胞生成会被消除。我们认为，靶向表达显性负性亮氨酸拉链蛋白是一种普遍适用于在小鼠中消除特定组织的方法。
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