Helix-loop-helix transcription factors mediate activation and repression of the p75LNGFR gene.
Helix-loop-helix transcription factors mediate activation and repression of the p75LNGFR gene.
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螺旋-环-螺旋转录因子介导 p75LNGFR 基因的激活和抑制。
DOI：
10.1128/mcb.15.11.6036
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发表时间：
1995
影响因子：
5.3
通讯作者：
Neuman,T
中科院分区：
文献类型：
--
作者：
Chiaramello,A;Neuman,K;Palm,K;Metsis,M;Neuman,T
大鼠和人类低亲和力神经生长因子受体p75 LNGFR基因启动子区的序列分析显示，一个单一的E-box顺式作用元件，位于上游的主要转录起始位点。E-box序列的缺失分析表明，它显着贡献top 75 LNGFR启动子活性。该E盒具有双重功能，它介导p75 LNGFR启动子活性的激活或抑制，这取决于相互作用的转录因子。我们发现，A类碱性螺旋-环-螺旋（bHLH）转录因子ME 1（ME 1a和ME 1b）的两种亚型，人类HEB转录因子的小鼠同源物，特异性repressp 75 LNGFR启动子活性。这种抑制可以通过HLH Id 2转录调节因子的共表达来释放。体外分析表明，ME 1a与p75 LNGFRE盒形成稳定的复合物，并可能与激活的E-box结合蛋白竞争。通过使用ME 1a过表达的PC 12细胞，我们表明内源性p75 LNGFR基因是ME 1a阻遏的靶点。总之，这些数据表明p75 LNGFRE盒和相互作用的bHLH转录因子参与了p75 LNGFR基因表达的调节。这些结果还表明，A类bHLH转录因子可以抑制和Id样负调控因子可以刺激基因表达。
Sequence analysis of rat and human low-affinity nerve growth factor receptorp75LNGFRgene promoter regions revealed a single E-boxcis-acting element, located upstream of the major transcription start sites. Deletion analysis of the E-box sequence demonstrated that it significantly contributes top75LNGFRpromoter activity. This E box has a dual function; it mediates either activation or repression of thep75LNGFRpromoter activity, depending on the interacting transcription factors. We showed that the two isoforms of the class A basic helix-loop-helix (bHLH) transcription factor ME1 (ME1a and ME1b), the murine homolog of the human HEB transcription factor, specifically repressp75LNGFRpromoter activity. This repression can be released by coexpression of the HLH Id2 transcriptional regulator. In vitro analyses demonstrated that ME1a forms a stable complex with thep75LNGFRE box and likely competes with activating E-box-binding proteins. By using ME1a-overexpressing PC12 cells, we showed that the endogenousp75LNGFRgene is a target of ME1a repression. Together, these data demonstrate that thep75LNGFRE box and the interacting bHLH transcription factors are involved in the regulation ofp75LNGFRgene expression. These results also show that class A bHLH transcription factors can repress and Id-like negative regulators can stimulate gene expression.