Identification of the promoter region of human interleukin 1 type I receptor gene: multiple initiation sites, high G+C content, and constitutive expression.

Identification of the promoter region of human interleukin 1 type I receptor gene: multiple initiation sites, high G+C content, and constitutive expression.
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人白细胞介素1I型受体基因启动子区的鉴定:多起始位点、高GC含量、组成型表达。

DOI:
10.1073/pnas.90.6.2295
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发表时间:
1993
影响因子:
11.1
通讯作者:
Clark,BD
Clark,BD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ye,K;Dinarello,CA;Clark,BD

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为了更好地了解白细胞介素1(IL-1)及其受体在疾病中的作用,我们分离了人IL-1 I型受体的基因组克隆,并鉴定了启动子区域。如引物延伸所示,存在多个转录起始位点。DNA序列分析表明,该启动子区既不含TATA盒,也不含CAAT盒,但5'上游调控元件含有两个AP-1样结合位点。在5'转录起始位点下游发现的内部调控序列含有4个Sp1结合结构域,并且具有75%的高G+C含量。mRNA的5'非翻译区的这一部分可以形成稳定的二级结构,如计算机建模所预测的。碱基对-4至+10与指导某些无TATA基因的基础表达的起始序列有着惊人的相似性-例如,淋巴细胞末端脱氧核苷酸转移酶。IL-1受体启动子指导瞬时转染细胞中氯霉素乙酰转移酶的基础表达。总的来说,IL-1 I型受体基因的启动子类似于具有管家和/或生长相关功能的组成型表达基因的启动子。启动子的组成性可以解释该基因在不同细胞类型中以低水平表达。我们的发现使我们对IL-1受体在健康和疾病中的调节机制有了更多的了解。
To better understand the role of interleukin 1 (IL-1) and its receptor in disease, we have isolated a genomic clone of the human IL-1 type I receptor and have identified the promoter region. There are multiple transcriptional initiation sites as demonstrated by primer extension. DNA sequence analysis shows that the promoter region contains neither a TATA nor a CAAT box; however, the 5' upstream regulatory elements contain two AP-1-like binding sites. The internal regulatory sequences found immediately downstream to the 5' transcriptional start site contain four Sp1 binding domains and have a high G+C content of 75%. This portion of the 5' untranslated region of the mRNA can form stable secondary structure as predicted by computer modeling. Base pairs -4 to + 10 share striking resemblance to an initiator sequence that directs basal expression of certain TATA-less genes-e.g., terminal deoxynucleotidyltransferase in lymphocytes. The IL-1 receptor promoter directs basal expression of chloramphenicol acetyltransferase in transiently transfected cells. Overall, the promoter of the IL-1 type I receptor gene resembles that of constitutively expressed genes that have housekeeping- and/or growth-related functions. The constitutive nature of the promoter may account for this gene being expressed at low levels in diverse cell types. Our finding sheds more understanding into the mechanisms governing the regulation of the IL-1 receptor in health and disease.
组成型启动子指导神经生长因子受体基因的表达。
DOI: 10.1128/mcb.8.8.3160-3167.1988
发表时间: 1988
影响因子: 5.3
作者:
Sehgal,A;Patil,N;Chao,M
通讯作者: Chao,M