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首页> 外文期刊>Molecular and Cellular Biology >Flanking sequences modulate the cell specificity of M-CAT elements.
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Flanking sequences modulate the cell specificity of M-CAT elements.

机译：侧翼序列调节M-CAT元件的细胞特异性。

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摘要

M-CAT elements mediate both muscle-specific and non-muscle-specific transcription. We used artificial promoters to dissect M-CAT elements derived from the cardiac troponin T promoter, whose regulation is highly striated muscle specific. We show that muscle-specific M-CAT-dependent expression requires two distinct components: the core heptameric M-CAT motif (5'-CATTCCT-3'), which constitutes the canonical binding site for TEF-1-related proteins, and specific sequences immediately flanking the core motif that bind an additional factor(s). These factors are found in higher-order M-CAT DNA-protein complexes with TEF-1 proteins. Non-muscle-specific promoters are produced when the sequences flanking the M-CAT motif are removed or modified to match those of non-muscle-specific promoters such as the simian virus 40 promoter. Moreover, a mutation of the 5'-flanking region of the cardiac troponin T M-CAT-1 element upregulated expression in nonmuscle cells. That mutation also disrupts a potential E box that apparently does not bind myogenic basic helix-loop-helix proteins. We propose a model in which M-CAT motifs are potentially active in many cell types but are modulated through protein binding to specific flanking sequences. In nonmuscle cells, these flanking sequences bind a factor(s) that represses M-CAT-dependent activity. In muscle cells, on the other hand, the factor(s) binding to these flanking sequences contributes to both the cell specificity and the overall transcriptional strength of M-CAT-dependent promoters.
机译：M-CAT元素介导肌肉特异性和非肌肉特异性转录。我们使用人工启动子来解剖源自心肌肌钙蛋白T启动子的M-CAT元件，其调节是高度横纹肌特异性的。我们表明，肌肉特异性M-CAT依赖性表达需要两个不同的成分：核心七聚体M-CAT模体（5'-CATTCCT-3'），它构成TEF-1相关蛋白的规范结合位点，以及特异性紧接在核心基序侧翼的，与其他因子结合的序列。这些因素存在于与TEF-1蛋白更高级的M-CAT DNA-蛋白复合物中。当去除或修饰M-CAT基序侧翼的序列以匹配非肌肉特异性启动子例如猿猴病毒40启动子的序列时，产生非肌肉特异性启动子。此外，心肌肌钙蛋白TMM-CAT-1元件的5'侧翼区的突变上调了非肌肉细胞的表达。该突变也破坏了可能不结合肌原性基本螺旋-环-螺旋蛋白的潜在E盒。我们提出了一个模型，其中M-CAT基序在许多细胞类型中都可能具有活性，但通过与特定侧翼序列结合的蛋白质进行调节。在非肌肉细胞中，这些侧翼序列结合了抑制M-CAT依赖性活性的因子。另一方面，在肌肉细胞中，与这些侧翼序列结合的因子有助于细胞特异性和M-CAT依赖性启动子的整体转录强度。

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