Human γ-globin genes silenced independently of other genes in the β-globin locus
Human γ-globin genes silenced independently of other genes in the β-globin locus
复制标题
人类 γ 珠蛋白基因独立于 β 珠蛋白基因座中的其他基因而沉默
作者：
N. Dillon;F. Grosveld
人类发育过程中红细胞生成的特征是从胚胎阶段到胎儿阶段再到成年阶段的过渡期间β样珠蛋白基因表达的转变。基因的激活和高水平表达由基因座控制区 (LCR) 指导，该区域位于 ɛ 基因 1-3 的 5' 处。 LCR 的位置及其在指导球蛋白基因高水平表达中的作用表明，β 基因与 LCR 相互作用的竞争在成年期胎儿 γ 基因沉默中发挥着重要作用4,5。我们现在已经构建了含有与 LCR 连接的人类 Aγ 珠蛋白基因的转基因小鼠品系。我们观察到转基因在胚胎阶段的高水平表达，但在成年动物中该基因的沉默。我们得出的结论是，γ 基因不会因 LCR 的存在而失调，并且成人生活中 γ 基因的沉默不需要来自 β 基因的竞争。因此，沉默可能是由与紧邻基因侧翼的序列结合的阶段特异性因子介导的。
ERYTHROPOIESIS during human development is characterized by switches in expression of β-like globin genes during the transition from the embryonic through fetal to adult stages. Activation and high-level expression of the genes is directed by the locus control region (LCR), located 5′ to the ɛ gene1–3. The location of the LCR and its role in directing high-level expression of the globin genes has led to the suggestion that competition from the β gene for interaction with the LCR has a major role in silencing the fetal γ genes during adult life4,5. We have now constructed lines of transgenic mice containing the human Aγ globin gene linked to the LCR. We observe high-level expression of the transgene in the embryonic stages but silencing of the gene in adult animals. We conclude that the γ gene is not deregulated by the presence of the LCR and that competition from the β gene is not required for silencing of the γ genes in adult life. The silencing is therefore likely to be mediated by stage-specific factors binding to sequences immediately flanking the genes.
单个红细胞特异性 DNase I 超敏感位点可激活转基因小鼠中高水平的人类 β-珠蛋白基因表达。
影响因子：
10.5
作者：
Ryan,TM;Behringer,RR;Martin,NC;Townes,TM;Palmiter,RD;Brinster,RL
通讯作者：
Brinster,RL
DOI：
10.1073/pnas.86.14.5439
发表时间：
1989-07-01
影响因子：
11.1
作者：
FORRESTER, WC;NOVAK, U;GROUDINE, M
通讯作者：
GROUDINE, M
胎儿血红蛋白遗传性持久性和 (delta beta) (0)-地中海贫血中的球蛋白基因表达。
DOI：
--
发表时间：
1988
期刊：
Oxford surveys on eukaryotic genes
影响因子：
--
作者：
Poncz,M;Henthorn,P;Stoeckert,C;Surrey,S
通讯作者：
Surrey,S