Cell-specific expression of the prolactin gene in transgenic mice is controlled by synergistic interactions between promoter and enhancer elements.
Cell-specific expression of the prolactin gene in transgenic mice is controlled by synergistic interactions between promoter and enhancer elements.
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转基因小鼠中催乳素基因的细胞特异性表达是由启动子和增强子元件之间的协同相互作用控制的。
DOI：
10.1101/gad.3.7.959
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发表时间：
1989
影响因子：
10.5
通讯作者：
Michael G. Rosenfeld
中科院分区：
文献类型：
--
作者：
E. Crenshaw;Kristin A. Kalla;D. Simmons;Larry W. Swanson;Michael G. Rosenfeld
催乳素基因的表达仅限于垂体前叶的哺乳细胞和生长激素细胞。在转基因小鼠中，由3kb的催乳素5‘侧翼区与萤火虫荧光素酶或人生长激素(HGH)报告基因融合而成的融合基因高水平表达，具有内源性催乳素基因严格的组织和细胞类型特异性。高水平的表达需要两个顺式作用区域：远端增强子(-1.8~-1.5 kb)和近端区域(-422~+33 bp)。在转基因小鼠中，这些区域中的每一个都可以将低水平的融合基因表达导向产生催乳素的细胞类型，但这些区域之间的协同作用对于高水平的表达是必要的。催乳素转基因表达的个体发生与高水平的POU同源结构域转录因子Pit-1的出现密切相关，Pit-1已被证明在远端增强子和近端区域结合结构相关序列，并在体外激活催乳素基因的表达。出乎意料的是，含有从正常环境中移除的远端增强子的转基因在产生催乳素的乳汁滋养细胞和产生促甲状腺激素(TSH)的促甲状腺激素细胞中都有表达，因此表明该增强子两侧的序列对于将表达限制在脑垂体内正确的细胞类型是必要的。这些数据表明，不同的基因激活和限制过程对于器官内特定细胞类型的表达是必要的。
Prolactin gene expression is restricted to the lactotrophic and somatomammotrophic cells of the anterior pituitary. In transgenic mice, a fusion gene consisting of 3 kb of prolactin 5'-flanking region fused to a firefly luciferase or human growth hormone (hGH) reporter gene is expressed at high levels with the strict tissue and cell-type specificity that is characteristic of the endogenous prolactin gene. High levels of expression require two cis-acting regions: a distal enhancer (-1.8 to -1.5 kb) and a proximal region (-422 to +33 bp). Each of these regions alone can direct low levels of fusion gene expression to prolactin-producing cell types in transgenic mice, but a synergistic interaction between these regions is necessary for high levels of expression. The ontogeny of the prolactin transgene expression closely follows the appearance of high levels of a POU homeo-domain transcription factor, Pit-1, that has been shown previously to bind structurally related sequences in both the distal enhancer and proximal regions and to activate the expression of the prolactin gene in vitro. Unexpectedly, transgenes containing the distal enhancer removed from its normal context are expressed in both the prolactin-producing lactotrophs and the thyroid-stimulating hormone (TSH)-producing thyrotrophs, thereby suggesting that sequences flanking this enhancer are necessary to restrict expression to the correct cell type within the pituitary. These data indicate that distinct processes of gene activation and restriction are necessary for the fidelity of cell-type-specific expression within an organ.
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影响因子：
4.1
作者：
SWANSON, LW;SAWCHENKO, PE;VALE, WW
通讯作者：
VALE, WW
通过细胞融合鉴定与正反式作用因子相互作用的基因序列。
DOI：
10.1126/science.3474782
发表时间：
1987
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lufkin,T;Bancroft,C
通讯作者：
Bancroft,C
GH3 垂体无细胞提取物对大鼠催乳素基因的选择性转录和 DNase I 保护。
DOI：
10.1073/pnas.84.15.5211
发表时间：
1987
影响因子：
11.1
作者：
Gutierrez-Hartmann,A;Siddiqui,S;Loukin,S
通讯作者：
Loukin,S
影响因子：
10.5
作者：
BEHRINGER, RR;MATHEWS, LS;BRINSTER, RL
通讯作者：
BRINSTER, RL
DOI：
10.1073/pnas.85.3.836
发表时间：
1988-02-01
影响因子：
11.1
作者：
BRINSTER, RL;ALLEN, JM;PALMITER, RD
通讯作者：
PALMITER, RD