Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene
Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene
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DOI：
10.1074/jbc.271.39.24105
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发表时间：
1996-09-27
影响因子：
4.8
通讯作者：
Markova, NG
中科院分区：
文献类型：
--
作者：
Jang, SI;Steinert, PM;Markova, NG
人聚丝蛋白原基因在表皮终末分化后期的颗粒层中表达。在体外转录实验中，我们表明 mRNA 的丰度和表达的特异性主要在转录水平上受到调节。我们发现 5' 侧翼序列以角质形成细胞特异性模式控制转录，并且 mRNA 起始位点之前只要 116 个碱基对就足以在体外限制转录至表皮细胞。这种特异性主要取决于-77 位激活蛋白 1 (AP1) 基序的存在。 c-jun/c-fos 异二聚体与该序列的结合赋予报告构建体在培养的表皮角质形成细胞中高水平的表达，而在 HeLa 细胞中几乎没有影响。 c-jun 的反式激活特性在此过程中至关重要。另一方面，junB 和 junD 参与早期表皮分化标记物转录的反式激活，通过不依赖于 AP1 位点直接结合且不具有细胞类型特异性的途径控制聚丝蛋白原表达。这些数据表明 AP1 因子参与丝聚合蛋白原基因表达的复杂、多途径调节。
The human profilaggrin gene is expressed in the granular layer during the late stages of terminal differentiation of the epidermis. In in vitro transcription experiments we show that the abundance of the mRNA and the specificity of the expression are regulated primarily at the level of transcription. We found that the 5'-flanking sequences control the transcription in a keratinocyte-specific mode and that as little as 116 base pairs preceding the mRNA initiation site is sufficient to restrict the transcription to epidermal cells in vitro. This specificity depends critically on the presence of an activator protein 1 (AP1) motif at position -77. Binding of c-jun/c-fos heterodimers to this sequence confers high levels of expression to the reporter constructs in cultured epidermal keratinocytes, while having little effect in HeLa cells. The transactivating properties of c-jun are essential in this process. On the other hand, junB and junD, which are involved in transactivating the transcription of earlier epidermal differentiation markers, control profilaggrin expression through a pathway which does not depend on a direct binding at the AP1 site and is not cell-type specific. These data indicate that AP1 factors are involved in a complex, multipathway regulation of the profilaggrin gene expression.