TRANSCRIPTIONAL ACTIVATION OF THE MELANOCYTE-SPECIFIC GENES BY THE HUMAN HOMOLOG OF THE MOUSE MICROPHTHALMIA PROTEIN
TRANSCRIPTIONAL ACTIVATION OF THE MELANOCYTE-SPECIFIC GENES BY THE HUMAN HOMOLOG OF THE MOUSE MICROPHTHALMIA PROTEIN
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DOI：
10.1093/jb/118.5.874
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发表时间：
1995-11-01
影响因子：
2.7
通讯作者：
SHIBAHARA, S
中科院分区：
文献类型：
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作者：
YASUMOTO, K;MAHALINGAM, H;SHIBAHARA, S
MI蛋白编码于小鼠小眼球(Mi)基因，是一种基本的螺旋-环-螺旋/亮氨酸拉链结构的转录因子。为了评价人类Mi蛋白同源物小眼球相关转录因子(MITF)的功能，我们分析了MITF对小鼠酪氨酸酶和酪氨酸酶相关蛋白1(TRP-I)基因启动子功能的影响，这两个基因启动子能够优先在黑色素产生细胞中转录，并且这两个启动子中都保守有一个11bp的增强子元件M box，其中包含一个CATGTG基序。通过瞬时表达分析，我们将负责色素细胞特异性表达的酪氨酸酶基因的顺式作用元件定位在82bp附近，该区域含有CATGTG基序(-12至-7位)，但缺少M盒(-107至-97位)。我们还提供了MITF反式激活酪氨酸酶启动子的82个碱基区和M盒的证据，并且M盒在体外被MITF结合。此外，MITF可能通过M盒(-44~-34位)激活Trp-1基因启动子。这些结果表明，MITF是调节色素细胞特异性基因转录的共同因子。
Mi protein encoded at the mouse microphthalmia (mi) locus is a transcription factor with a basic helix-loop-helix/leucine zipper structure. To assess the function of the human homolog of Mi protein, termed microphthalmia-associated transcription factor (MITF), we analyzed the effects of MITF on the promoter function of the mouse tyrosinase and tyrosinase-related protein 1 (TRP-I) genes, These two gene promoters are able to direct transcription preferentially in melanin-producing cells, and an enhancer element M box of 11 bp, containing a CATGTG motif, is conserved in both promoters. By transient expression assays, we have localized the cis-acting element of the tyrosinase gene responsible for pigment cell-specific expression to the proximal 82-bp region, which contains a CATGTG motif (positions -12 to -7) but lacks the M box (positions -107 to -97). We also provide evidence that the 82-bp region and the M box are involved in the transactivation of the tyrosinase promoter by MITF and that the M box is bound by MITF in vitro. Furthermore, MITF activated the TRP-1 gene promoter possibly through the M box (positions -44 to -34). These results suggest that MITF is a common factor regulating transcription of the pigment cell-specific genes.