Overlapping positive and negative regulatory elements determine lens-specific activity of the delta 1-crystallin enhancer
Overlapping positive and negative regulatory elements determine lens-specific activity of the delta 1-crystallin enhancer
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重叠的正负调节元件决定了 Delta 1-晶状体蛋白增强剂的晶状体特异性活性
DOI：
10.1128/mcb.13.9.5206-5215.1993
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发表时间：
1993
影响因子：
5.3
通讯作者：
Hisato Kondoh
中科院分区：
文献类型：
--
作者：
Y. Kamachi;Hisato Kondoh
δ1-晶状体蛋白基因的晶状体特异性表达由第三个内含子中的增强子控制，并且发现30bp长的DC5片段负责引发晶状体特异性活性。 DC5 片段的突变分析鉴定出两个连续的、相互依赖的正元件和一个与位于 3' 的正元件重叠的负元件。先前鉴定出的普遍存在的因子 delta EF1 与负元件结合并抑制非晶状体细胞中的增强子活性。突变和共转染分析表明存在一种激活剂，该激活剂可能通过结合位点竞争来抵消晶状体细胞中 delta EF1 的作用。我们还发现了一组核因子，统称为 delta EF2，它与位于 5' 的正元素结合。 delta EF2a和-b是晶状体细胞中的主要种类，而delta EF2c和-d在非晶状体细胞中占主导地位。这些 delta EF2 蛋白可能与 3' 位置元件结合的因子协同作用，激活晶状体细胞并抑制非晶状体细胞。 δ EF2 蛋白还与 γ F-晶状体蛋白基因的启动子序列结合，表明 δ EF2 蛋白参与各种晶状体蛋白类别的晶状体特异性调节。
Lens-specific expression of the delta 1-crystallin gene is governed by an enhancer in the third intron, and the 30-bp-long DC5 fragment was found to be responsible for eliciting the lens-specific activity. Mutational analysis of the DC5 fragment identified two contiguous, interdependent positive elements and a negative element which overlaps the 3'-located positive element. Previously identified ubiquitous factors delta EF1 bound to the negative element and repressed the enhancer activity in nonlens cells. Mutation and cotransfection analyses indicated the existence of an activator which counteracts the action of delta EF1 in lens cells, probably through binding site competition. We also found a group of nuclear factors, collectively called delta EF2, which bound to the 5'-located positive element. delta EF2a and -b were the major species in lens cells, whereas delta EF2c and -d predominated in nonlens cells. These delta EF2 proteins probably cooperate with factors bound to the 3'-located element in activation in lens cells and repression in nonlens cells. delta EF2 proteins also bound to a promoter sequence of the gamma F-crystallin gene, suggesting that delta EF2 proteins are involved in lens-specific regulation of various crystallin classes.
影响因子：
10.5
作者：
STURM, RA;DAS, G;HERR, W
通讯作者：
HERR, W
通过差异剪接产生的转录激活子 mTFE3 的显性失活形式。
DOI：
10.1126/science.1840705
发表时间：
1991
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Roman,C;Cohn,L;Calame,K
通讯作者：
Calame,K