Phinney D G, Tseng S W, Hall B, Ryder K
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19007, USA.
Oncogene. 1996 Nov 7;13(9):1875-83.
The junB locus contains nine flanking evolutionarily conserved sequences (FECS) that share 72% to 91% sequence identity between human and mouse. These FECS encompass the same regions of flanking DNA necessary for maximal mitogenic induction of junB. Most of the cis elements reported to date that affect junB regulation also reside within FECS. These observations suggest that the persistence of FECS through evolution reflects a necessary role in junB transcriptional regulation. In this report, we identify specific regulatory cis elements within junB FECS II and III and provide a quantitative analysis of the contribution made by these sequences to junB induction. These cis elements include a Serum Response Element (SRE), two Ets sites previously unrecognized as contributing to junB expression, and two novel Ets-linked motifs (ELMs). In general, mutating any single element significantly impairs junB induction. Moreover, the same mutations alter the structure of junB 5' flanking DNA within chromatin. Collectively, these results suggest that multiple proteins bound within FECS confederate to form a functional promoter complex, the activity of which is dependent upon a specific chromatin architecture.
junB基因座包含九个侧翼进化保守序列（FECS），人类和小鼠之间的序列同一性为72%至91%。这些FECS包含junB最大促有丝分裂诱导所需的侧翼DNA的相同区域。迄今为止报道的大多数影响junB调控的顺式元件也位于FECS内。这些观察结果表明，FECS在进化过程中的持续存在反映了其在junB转录调控中的必要作用。在本报告中，我们鉴定了junB FECS II和III内的特定调控顺式元件，并对这些序列对junB诱导的贡献进行了定量分析。这些顺式元件包括一个血清反应元件（SRE）、两个先前未被认为对junB表达有贡献的Ets位点以及两个新的Ets连接基序（ELM）。一般来说，突变任何单个元件都会显著损害junB诱导。此外，相同的突变会改变染色质内junB 5'侧翼DNA的结构。总的来说，这些结果表明，FECS内结合的多种蛋白质联合形成一个功能性启动子复合物，其活性取决于特定的染色质结构。
