Identification of the functional elements in the bidirectional promoter of the mouse O-sialoglycoprotein endopeptidase and APEX nuclease genes

Identification of the functional elements in the bidirectional promoter of the mouse O-sialoglycoprotein endopeptidase and APEX nuclease genes
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DOI:
10.1016/s0006-291x(02)00939-7
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发表时间:
2002-08-30
影响因子:
3.1
通讯作者:
Seki, S
Seki, S
中科院分区:
生物学4区
文献类型:
--
作者:
Ikeda, S;Ayabe, H;Seki, S

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哺乳动物O-唾液酸糖蛋白内肽酶(Osgep)的基因与APEX核酸酶(Apex)(一种多功能DNA修复酶)的基因以头对头方向紧邻。为了阐明这些不同基因的调控,我们用荧光素酶报告基因研究了它们的启动子区。含有整个小鼠Apex基因的片段的缺失分析表明,驱动Osgep方向的顺式作用元件广泛分布在mApex基因中,处于反义方向。我们详细研究了mOsgep转录起始位点附近的顺式作用元件。mOsgep和mApex之间的间隔序列显示出具有双向启动子活性,并且已经报道两个CCAAT盒在mApex方向上促进基础转录。然而,只有一个CCAAT盒接近的转录起始位点的mOsgep是重要的转录mOsgep。一个Sp1结合序列被发现参与双向转录,一个CRE/ATF样序列被证明作为mOsgep转录的阻遏物。定量RT-PCR结果显示,mApex和mOsgep基因在所有组织中均有表达,mOsgep的表达量较mApex低。(C)2002 Elsevier Science(美国)。All rights reserved.
The gene for mammalian O-sialoglycoprotein endopeptidase (Osgep) lies immediately adjacent to the gene for the APEX nuclease (Apex), a multifunctional DNA repair enzyme, in a head-to-head orientation. To clarify the regulation of these divergent genes, we studied their promoter regions with luciferase reporters. Deletion analysis of a fragment containing the entire mouse Apex gene suggested that cis-acting elements driving in the direction of Osgep are widely distributed in the mApex gene, in the antisense orientation. We investigated in detail cis-acting elements near the transcription initiation site of mOsgep. The spacer sequence between mOsgep and mApex was shown to have bidirectional promoter activity and it has been reported that two CCAAT boxes promote basal transcription in the direction of mApex. However, only one of the CCAAT boxes proximal to the transcription initiation site of mOsgep was important for transcription towards mOsgep. An Sp1-binding sequence was found to be involved in bidirectional transcription and a CRE/ATF-like sequence was shown to function as a repressor of mOsgep transcription. Quantitative RT-PCR showed that the mApex and mOsgep genes were expressed in all tissues examined and that expression of mOsgep was low compared with mApex. (C) 2002 Elsevier Science (USA). All rights reserved.