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Journal of Biochemistry Advance Access originally published online on December 6, 2008
Journal of Biochemistry 2009 145(3):279-288; doi:10.1093/jb/mvn165
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© The Authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

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

Yasuhiro Imamura1, Yoshihisa Fujigaki2, Yuriko Oomori3, Ken Ouryouji4, Shigeru Yanagisawa2, Hiroo Miyazawa4 and Pao-Li Wang1,*

1Department of Pharmacology, Matsumoto Dental University; 2Department of Oral Preventive Dentistry, Matsumoto Dental University; 3Department of Oral Health Promotion, Graduate school of Oral Medicine, Matsumoto Dental University; and 4Department of Pediatric Dentistry, Matsumoto Dental University, 1780 Gohbara, Hiro-oka, Shiojiri, Nagano 399-0781, Japan

*To whom correspondence should be addressed: Tel/Fax: +81-263-51-2102, E-mail: ohhourei{at}po.mdu.ac.jp

Received November 8, 2008; Accepted November 21, 2008


  Abstract

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.

Key Words: DNA-binding proteins, histatin, positive regulatory element, saliva, transcriptional regulation

Abbreviations: DMEM, Dulbecco's modified Eagle medium; FBS, fetal bovine serum; HSG, human salivary gland; MEME, minimum essential medium Eagle

{dagger}The nucleotide sequence reported in this article has been submitted to the DDBJ with accession number AB430585.


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