Interferon-γ Induction of the Human Leukocyte Antigen-E Gene Is Mediated through Binding of a Complex Containing STAT1α to a Distinct Interferon-γ-responsive Element*
Interferon-γ Induction of the Human Leukocyte Antigen-E Gene Is Mediated through Binding of a Complex Containing STAT1α to a Distinct Interferon-γ-responsive Element*
复制标题
人类白细胞抗原 E 基因的干扰素 γ 诱导是通过含有 STAT1α 的复合物与独特的干扰素 γ 响应元件结合介导的*
DOI：
--
复制
发表时间：
1996
影响因子：
4.8
通讯作者：
G. Ginder
中科院分区：
文献类型：
--
作者：
K. Gustafson;G. Ginder
人类主要组织相容性复合体I类基因的表达先前已被证明在干扰素-γ(干扰素-γ)暴露后在转录水平上增加。在这份报告中，我们研究了干扰素-γ诱导人类MHC-I类基因HLAE转录的分子机制。对HLAE启动子控制下的CAT报告基因结构的功能分析表明，U937细胞中存在一个独特的干扰素-γ反应元件，称为干扰素反应区，它是介导干扰素-γ应答的必要条件和充分条件。这个顺式作用的调控序列包含一个不完全的反向重复序列；IRR的5‘-一半类似于干扰素-γ激活位点(GAS)，而3’-一半类似于干扰素刺激反应元件(ISRE)。凝胶迁移率改变分析表明，IRR结合了单一的、特异性的干扰素-γ诱导的复合体(IRR-AC)，该复合体在干扰素-γ处理后迅速形成，并且不依赖于蛋白质的合成。与来自其他干扰素诱导基因的GAS和ISRE序列的竞争实验表明，GAS序列竞争IRR-AC，而ISRE序列不竞争。突变分析表明，IRR的5‘-半区或3’-半区的点突变阻止了复合体的结合，并取消或显著降低了报告基因结构的干扰素-γ反应性。SuperShift分析表明，IRR-AC含有一种针对信号转导和转录激活因子α(信号转导和转录激活因子)的抗体所识别的因子。综上所述，这些发现表明，干扰素-γ诱导人类白细胞抗原-E基因转录的机制与其他MHC-I类基因的机制不同。
Expression of the human major histocompatibility complex (MHC) class I genes has been shown previously to increase at the transcriptional level following exposure to interferon-γ (IFN-γ). In this report we have examined the molecular mechanisms involved in the IFN-γ-induced transcription of the human MHC class I gene, HLA-E. Functional analysis of CAT reporter gene constructs under the control of the HLA-E promoter transfected into U937 cells revealed the presence of a distinct IFN-γ-responsive element, termed the interferon response region (IRR), that was necessary and sufficient to mediate the response to IFN-γ. This cis-acting regulatory sequence contains an imperfect inverted repeat; the 5′-half of the IRR resembles the IFN-γ activation site (GAS), and the 3′-half of the IRR resembles the interferon-stimulated response element (ISRE). Gel mobility shift assays demonstrated that the IRR bound a single, specific, IFN-γ-induced complex (IRR-AC), which was formed rapidly following treatment with IFN-γ and was independent of protein synthesis. Competition experiments with GAS and ISRE sequences from other IFN-inducible genes showed that GAS sequences competed for the IRR-AC, whereas ISRE sequences did not compete. Mutational analysis demonstrated that point mutations in either the 5′-half or 3′-half of the IRR prevented binding of the complex and abrogated or markedly reduced the IFN-γ responsiveness of reporter gene constructs. Supershift analysis revealed that the IRR-AC contains a factor that was recognized by antibodies specific for the protein STAT1α (signal transducer and activator of transcription). Taken together, these findings suggest that the mechanism of IFN-γ-induced transcription of the HLA-E gene is distinct from that of other MHC class I genes.
登录
查看更多内容
DOI：
--
发表时间：
1988
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Koller,BH;Geraghty,DE;Shimizu,Y;DeMars,R;Orr,HT
通讯作者：
Orr,HT
影响因子：
56.9
作者：
SHUAI, K;STARK, GR;DARNELL, JE
通讯作者：
DARNELL, JE
影响因子：
7.5
作者：
Ke Shuai
通讯作者：
Ke Shuai
DOI：
10.1016/s0021-9258(19)51096-1
发表时间：
1994-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Raz;J. Durbin;D. Levy
通讯作者：
R. Raz;J. Durbin;D. Levy
DOI：
10.1073/pnas.90.9.4314
发表时间：
1993-05-01
影响因子：
11.1
作者：
PEARSE, RN;FEINMAN, R;RAVETCH, JV
通讯作者：
RAVETCH, JV