Activating transcription factor/cAMP response element binding protein family member regulated transcription of CD1A
Activating transcription factor/cAMP response element binding protein family member regulated transcription of CD1A
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DOI：
10.4049/jimmunol.177.10.7024
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Wang, Chyung-Ru
中科院分区：
文献类型：
--
作者：
Colmone, Angela;Li, Sha;Wang, Chyung-Ru
在皮质胸腺细胞和APC上特异性表达的Ag呈递分子中，CD 1a具有独特的表达模式。由于自身免疫性疾病、感染和肿瘤都可以导致CD 1a表达的改变，我们正试图描述CD 1A的转录调控，从而阐明CD 1A的特异性表达。在这项研究中，我们已经确定了一个最小的近端启动子区域所需的CD 1A转录。在该区域内的计算机搜索确定了许多淋巴特异性转录因子的潜在结合位点，包括ETS转录因子、C/EBP、加塔和CREB。缺失和位点特异性突变体分析显示，一个潜在的cAMP反应元件（CRE）965 bp的CD 1A翻译起始位点上游的关键作用。两个转录激活因子（ATF）/CREB家族成员，CREB-1和ATF-2，能够在体外和体内结合该位点。值得注意的是，ATF/CREB家族成员的活化降低了CD 1A转录，而ATF-2表达的降低导致CD 1A RNA水平的增加。这些因子也结合人单核细胞中的CD 1A启动子的事实强烈表明ATF/CREB家族成员在调节CD 1A表达中的作用。
CD1a has a unique expression pattern among Ag-presenting molecules, expressed specifically on cortical thymocytes; and APCs. As autoimmune disease, infection, and tumors can all result in alteration of CD1a expression, we are attempting to characterize the transcriptional regulation, and thus shed some light on specific expression, of CD1A. In this study, we have identified a minimal proximal promoter region required for CD1A transcription. Computer searches within this region identified numerous potential binding sites for lymphoid-specific transcription factors, including the ETS transcription factors, C/EBP, GATA, and CREB. Deletion and site-specific mutant analysis revealed a critical role of a potential cAMP response element (CRE) 965 bp upstream of the CD1A translation start site. Two activating transcription factor (ATF)/CREB family members, CREB-1 and ATF-2, are able to bind this site in vitro and in vivo. Notably, activation of ATF/CREB family members decreases CD1A transcription, while decrease in ATF-2 expression results in increased CDIA RNA level. The fact that these factors also bind the CD1A promoter in human monocytes strongly suggests a role for ATF/CREB family members in regulation of CDIA expression.