Transcriptional Regulation of the Salivary Histatin Gene: Finding of a Strong Positive Regulatory Element and Its Binding Protein

Transcriptional Regulation of the Salivary Histatin Gene: Finding of a Strong Positive Regulatory Element and Its Binding Protein
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DOI:
10.1093/jb/mvn165
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发表时间:
2009-03-01
影响因子:
2.7
通讯作者:
Wang, Pao-Li
Wang, Pao-Li
中科院分区:
生物学4区
文献类型:
--
作者:
Imamura, Yasuhiro;Fujigaki, Yoshihisa;Wang, Pao-Li

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组蛋白是在人类唾液腺中发现并表达的唾液蛋白。它们在非免疫系统的抗菌防御中发挥作用,例如,对抗白色念珠菌。组蛋白基因HIS1的转录调控序列长期以来一直不清楚。在这里,我们从人类基因组DNA中克隆了可能的启动子,并在荧光素酶报告系统中对其进行了测试。这种启动子在唾液腺细胞中比在其他类型的细胞中更活跃。对缺失突变体的分析表明,2254-1748区域是一个很强的正性转录元件,其功能核心序列(称为HTN27盒)与下游序列、680-28区域和近端启动子一起以正反向协同作用。正单链HTN27盒与HSG细胞中存在的100 kDa蛋白质特异性结合,但在HeLa细胞中不存在。这些发现表明,组蛋白基因表达的调节可能是错综复杂的,并且似乎在唾液腺细胞中具有细胞类型偏好。
Histatins are salivary proteins found and expressed in human salivary glands. They play a role in the non-immune system of antimicrobial defense, for instance, against Candida albicans. The transcriptional regulatory sequences of the histatin gene, HIS1, have remained obscure for a long time. Here, we cloned the putative promoter from human genomic DNA and tested it in a luciferase reporter system. This promoter is much more active in salivary gland cells than in other cell types. Analysis of deletion mutants revealed that the region encompassing 2254 to 1748 is a strong positive transcriptional element, and its functional core sequence (termed HTN27 box) works in correct and reverse orientations in synergy with downstream sequences, the region spanning 680 to 28 and a proximal promoter. The plus single-stranded HTN27 box is specifically bound by a 100 kDa protein that is present in HSG cells, but not in HeLa cells. These findings indicate that the regulation of the histatin gene expression may be intricate, and it seems to have a cell-type preference in the salivary gland cells.