Drolet D W, Scully K M, Simmons D M, Wegner M, Chu K T, Swanson L W, Rosenfeld M G
Eukaryotic Regulatory Biology Program, University of California, San Diego, La Jolla 92093-0648.
Genes Dev. 1991 Oct;5(10):1739-53. doi: 10.1101/gad.5.10.1739.
We have identified and characterized a new member of the leucine zipper (bZIP) gene family of transcription factors, thyrotroph embryonic factor (TEF). Analysis of the ontogeny of TEF gene expression reveals the presence of TEF transcripts, beginning on embryonic day 14, only in the region of the rat anterior pituitary gland in which thyrotrophs arise. This pattern of gene expression corresponds temporally and spatially to the onset of thyroid-stimulating hormone (TSH beta) gene expression, which defines the thyrotroph phenotype. Coupled with this observation, we find that TEF can bind to and trans-activate the TSH beta promoter. In contrast to this restricted pattern of expression during embryogenesis, TEF transcripts appear in several tissues in the mature organism. We propose that TEF belongs to a new class of bZIP proteins on the basis of the unique homology between TEF and another member of the bZIP gene family, the albumin D box-binding protein (DBP). TEF and DBP transcripts are coexpressed in a pituitary cell line, and these two proteins can readily form heterodimers. The DNA-binding and dimerization domains of TEF correspond to those found in other bZIP proteins. We have however, identified a cluster of basic amino acids, found only in TEF and DBP, that is necessary for the proper DNA-binding site specificity of TEF. A major trans-activation domain of TEF resides outside the region of homology to other bZIP proteins. These data are consistent with a role for a member of a new class of bZIP transcription factors in activating gene expression in the developing thyrotroph.
我们已经鉴定并表征了转录因子亮氨酸拉链（bZIP）基因家族的一个新成员——促甲状腺激素胚胎因子（TEF）。对TEF基因表达个体发生的分析表明，从胚胎第14天开始，TEF转录本仅存在于大鼠垂体前叶中促甲状腺细胞出现的区域。这种基因表达模式在时间和空间上与促甲状腺激素（TSHβ）基因表达的起始相对应，TSHβ基因表达定义了促甲状腺细胞表型。与此观察结果相结合，我们发现TEF可以结合并反式激活TSHβ启动子。与胚胎发育过程中这种受限的表达模式不同，TEF转录本出现在成熟生物体的多个组织中。基于TEF与bZIP基因家族的另一个成员白蛋白D盒结合蛋白（DBP）之间独特的同源性，我们提出TEF属于一类新的bZIP蛋白。TEF和DBP转录本在垂体细胞系中共表达，并且这两种蛋白质可以很容易地形成异源二聚体。TEF的DNA结合和二聚化结构域与其他bZIP蛋白中的结构域相对应。然而，我们已经鉴定出一组仅在TEF和DBP中发现的碱性氨基酸簇，这对于TEF正确的DNA结合位点特异性是必需的。TEF的一个主要反式激活结构域位于与其他bZIP蛋白同源区域之外。这些数据与一类新的bZIP转录因子成员在发育中的促甲状腺细胞中激活基因表达的作用一致。
