Organization, sequence, and expression of the murine S100 beta gene. Transcriptional regulation by cell type-specific cis-acting regulatory elements.
Organization, sequence, and expression of the murine S100 beta gene. Transcriptional regulation by cell type-specific cis-acting regulatory elements.
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鼠 S100 β 基因的组织、序列和表达。
DOI：
10.1016/s0021-9258(20)80754-6
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Dana C. Hilt
中科院分区：
文献类型：
--
作者：
Hao Jiang;Sanjiv Shah;Dana C. Hilt
报告了鼠 S100 β 基因表达的组织、序列和转录调控。该基因长度约为 9 KB，由三个外显子和两个内含子组成。推导的鼠 S100 β 蛋白序列与人类 S100 β 蛋白仅 1 个氨基酸不同。鼠S100β基因包含一个TATA盒（AATAA）和一个反向CCAAT盒（ATTGG），分别位于帽位点上游30个核苷酸和92个核苷酸处。跨越 TATA 盒和反向 CCAAT 盒的 149 个碱基对 DNA 片段 (-157/-9) 充当启动子。小鼠 S100 beta 启动子在神经胶质细胞 (C6) 中驱动的转录水平比非神经胶质细胞 (3T3) 细胞高 4 倍，表明启动子区域内存在潜在的细胞类型特异性调控元件。 5'-侧翼区域以方向无关的方式抑制同源 S100 β 以及异源 SV40 启动子的转录。然而，5'侧翼区域在抑制 S100 β 启动子依赖性转录时表现出细胞类型特异性，表明它参与了 S100 β 基因的细胞类型特异性表达。为了绘制细胞类型特异性调控元件图谱，在 C6 和 3T3 细胞中对 5' 区的各种缺失进行了转录分析。两种细胞类型特异性负调节元件，一种在非神经胶质细胞中活跃，另一种在神经胶质细胞中活跃，分别被映射到区域-1552/-1234和-1234/-551。强负调节元件和相对弱的负调节元件分别位于-551/-157和-1669/-1552区域。鼠S100β基因处于复杂的转录调控之下，涉及由包括细胞类型特异性元件在内的多个顺式作用调控元件的组合施加的强直负控制。
The organization, sequence, and transcriptional regulation of expression of the murine S100 beta gene are reported. The gene is approximately 9 kilobase pairs in length and is composed of three exons and two introns. The deduced murine S100 beta protein sequence differs from the human S100 beta protein by only 1 amino acid. The murine S100 beta gene contains a TATA box (AATAA) and a reverse CCAAT box (ATTGG) located at 30 nucleotides and 92 nucleotides upstream of the cap site, respectively. A 149-base pair DNA fragment (-157/-9) spanning the TATA box and the reverse CCAAT box functions as a promoter. The murine S100 beta promoter drives a 4-fold higher level of transcription in glial (C6) than in non-glial (3T3) cells, suggesting the existence of a potential cell type-specific regulatory element within the promoter region. The 5'-flanking region suppresses transcription from the homologous S100 beta as well as the heterologous SV40 promoters in an orientation-independent fashion. However, the 5'-flanking region exhibits cell type specificity when suppressing the S100 beta promoter-dependent transcription, indicating its involvement in the cell type-specific expression of S100 beta gene. In order to map cell type-specific regulatory elements, transcription analyses of various deletions of the 5'-region were carried out in C6 and 3T3 cells. Two cell type-specific negative regulatory elements, one active in non-glial cells and another active in glial cells, were mapped to the regions -1552/-1234 and -1234/-551, respectively. A strong negative regulatory element and a relatively weak negative element were located in the regions -551/-157 and -1669/-1552, respectively. The murine S100 beta gene is under complex transcriptional regulation involving tonic negative control exerted by combination of multiple cis-acting regulatory elements including cell type-specific elements.
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