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首页> 外文期刊>Journal of Cellular Physiology >Nectin-2 expression in testicular cells is controlled via the functional cooperation between transcription factors of the Sp1, CREB, and AP-1 families.
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Nectin-2 expression in testicular cells is controlled via the functional cooperation between transcription factors of the Sp1, CREB, and AP-1 families.

机译：Nectin-2睾丸细胞中表达通过控制功能之间的合作Sp1的转录因子,分子和AP-1家庭。

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Nectin-2, a major protein component of the adherens junctions (AJs), is found between Sertoli cells and germ cells in the seminiferous epithelium. Recent studies have shown that the expression of nectin-2 gene in testis is crucial to maintain normal spermatogenesis since male knockout mice lacking nectin-2 gene are sterile and possess morphologically abnormal spermatozoa. However, the molecular mechanisms governing its basal transcription remain poorly understood. By the use of Sertoli and germ cell-lines (TM4 and GC-2spd(ts) cells, respectively) in transient transfection studies, we showed that the minimal mouse nectin-2 promoter was located between nucleotides -316 and -211 (relative to the translation start site). Two putative Sp1 motifs and one each of the CRE, AP1, and AP2 motifs were identified within this region. Mutational studies showed that these two Sp1 motifs cooperated synergistically with the CRE motif, but not the AP1 and AP2 motifs, to regulate nectin-2 gene transcription in both TM4 and GC-2spd(ts) cells. By EMSAs, we found that an AP-1 consensus sequence was able to inhibit DNA-protein complex formation with the CRE motif, suggesting an interaction between the AP-1 transcription factor (c-Jun) and CREB within the CRE motif. Overexpressions of CREB and c-Jun, but not c-Fos, also significantly increased the promoter activity, which suggests that CREB and c-Jun are the crucial transcription factors involved in regulating nectin-2 gene transcription. Chromatin immunoprecipitation assay has shown that, in vivo, CREB, c-Jun, and Sp1 family proteins are bound to the mouse nectin-2 promoter. Analysis of the staged tubules has confirmed that the cyclic expressions of CREB and nectin-2 coincide with the event of adherens junction restructuring between Sertoli cells and germ cells. The cross-talk between CREB, c-Jun, and Sp1 family protein is believed to be a major transcription machinery to drive nectin-2 expression in Sertoli cells.
机译：Nectin-2,一个主要的蛋白质的组成部分(能),粘合连接处并且发现之间塞尔托利氏细胞和生殖细胞在精上皮细胞。nectin-2基因的表达在睾丸是至关重要的维持正常的精子发生因为男性基因敲除小鼠缺乏nectin-2无菌和拥有形态异常的精子。然而,管理它的分子机制基底转录仍然知之甚少。使用滋养和生殖细胞系(TM4和GC-2spd (ts)细胞,分别在瞬态)转染的研究中,我们表明,最小鼠标nectin-2位于启动子核苷酸(相对于-316人和-211人翻译开始网站)。和一个每个CRE AP1, AP2图案确定在这个地区。表明这两个Sp1主题合作CRE主题的增效剂,但不是AP1 AP2图案,调节nectin-2基因转录TM4和GC-2spd (ts)细胞。emsa,我们发现一个AP-1共识能够抑制dna蛋白质序列复杂形成的CRE主题,表明一个AP-1转录因子之间的相互作用(c-Jun)和分子内的CRE主题。超表达的分子和c-Jun,但不是c-Fos,也显著增加了启动子活动,这表明分子和c-Jun关键的转录因子参与调节nectin-2基因转录。免疫沉淀反应试验表明,体内,分子、c-Jun和Sp1家族蛋白绑定到鼠标nectin-2启动子。循环的上演了小管已确认分子的表达和nectin-2配合adherens结重组的事件支持细胞和生殖细胞之间。分子之间的相互作用,c-Jun, Sp1的家庭蛋白质被认为是一个主要的转录机械驱动nectin-2表达支持细胞。

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