Andreoli J M, Jang S I, Chung E, Coticchia C M, Steinert P M, Markova N G
Laboratory of Skin Biology, NIAMS, NIH, Bethesda, MD 20892-2752, USA.
Nucleic Acids Res. 1997 Nov 1;25(21):4287-95. doi: 10.1093/nar/25.21.4287.
Ets proteins have been implicated in the regulation of gene expression during a variety of biological processes, including growth control, differentiation, development and transformation. More than 35 related proteins containing the 'ets domain' have now been found which specifically interact with DNA sequences encompassing the core tetranucleotide GGAA. Although ets responsive genes have been identified in the epidermis, little is known about their distribution and function in this tissue. We have now demonstrated that epidermis and cultured epidermal keratinocytes synthesize numerous ets proteins. The expression of some of these proteins is regulated as a function of differentiation. Among these is a novel ets transcription factor with a dual DNA-binding specificity, which we have called jen. The expression of jen is not only epithelial specific, but it is the only ets protein so far described, and one of the very few transcription factors whose expression is restricted to the most differentiated epidermal layers. We show that two epidermal marker genes whose expression coincides with that of jen are transregulated by this protein in a complex mode which involves interactions with other transcriptional regulators such as Sp1 and AP1.
Ets蛋白已被证明在多种生物过程中参与基因表达的调控,这些过程包括生长控制、分化、发育和转化。目前已发现35种以上含有“ets结构域”的相关蛋白,它们能与包含核心四核苷酸GGAA的DNA序列特异性相互作用。尽管在表皮中已鉴定出ets反应基因,但对它们在该组织中的分布和功能了解甚少。我们现已证明,表皮和培养的表皮角质形成细胞能合成多种ets蛋白。其中一些蛋白的表达受分化调控。其中有一种具有双重DNA结合特异性的新型ets转录因子,我们将其命名为jen。jen的表达不仅具有上皮特异性,而且是迄今为止所描述的唯一一种ets蛋白,也是极少数其表达仅限于最分化表皮层的转录因子之一。我们发现,两个与jen表达一致的表皮标记基因受该蛋白以复杂模式反式调控,这种模式涉及与其他转录调节因子如Sp1和AP1的相互作用。