Studies of the H60a locus in C57BL/6 and 129/Sv mouse strains identify the H60a 3'UTR as a regulator of H60a expression.

Studies of the H60a locus in C57BL/6 and 129/Sv mouse strains identify the H60a 3'UTR as a regulator of H60a expression.
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C57BL/6和129/SV小鼠菌株中H60A基因座的研究识别H60A 3'UTR是H60A表达的调节剂。

DOI:
10.1016/j.molimm.2010.10.015
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发表时间:
2011-01
影响因子:
3.6
通讯作者:
Bui JD
Bui JD
中科院分区:
医学3区
文献类型:
--
作者:
Zhang H;Hardamon C;Sagoe B;Ngolab J;Bui JD

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次要组织相容性抗原60(H60a)在BALB/C和129/Sv小鼠中表达,而在C57BL/6小鼠中不表达。我们最近发现干扰素γ下调H60a的表达,但其调节机制尚不清楚。为了更好地了解H60a的调控,我们研究了H60a在129/Sv和C57BL/6菌株中的基因组位置。我们发现H60a的上游调控区在两个菌株中都存在并具有功能。有趣的是,干扰素γ可以下调129Sv小鼠细胞系中H60a的转录,但不能下调C57BL/6小鼠细胞系中H60a的转录,这表明干扰素γ对H60a的依赖调节是通过保守启动子区域以外的顺式元件进行的。我们确定干扰素γ对H60a的调节是通过H60a的3‘非编码区进行的,这在12 9/Sv细胞中存在,但不是C57BL/6细胞。我们还发现,H60a的3‘非编码区和microRNAs对H60a在肿瘤细胞系中的组成性表达水平有贡献。我们的结论是,在12 9/Sv株小鼠中,H60a可以通过干扰素γ和未知的microRNAs受到其3‘端非编码区的调控。由于H60a介导了NK细胞的靶点识别,我们的研究发现了一个可以调节病毒和肿瘤监视的顺式元件。
The minor histocompatibility antigen 60 (H60a) is expressed in BALB/C and 129/Sv but not in C57BL/6 strains of mice. We recently found that IFNγ down-regulates H60a, but the mechanism of regulation is not known. To better understand the regulation of H60a, we examined the genomic locus of H60a in 129/Sv and C57BL/6 strains. We found that the upstream regulatory region of H60a was present and functional in both strains. Interestingly, IFNγ can down-regulate H60a transcripts in cell lines from 129/Sv but not C57BL/6 strains of mice, suggesting that IFNγ-dependent regulation of H60a proceeds through cis elements other than the conserved promoter region. We determined that the regulation of H60a by IFNγ proceeds through the 3′UTR of H60a, which is present in 129/Sv, but not C57BL/6 cells. We also found that the H60a 3′UTR and microRNAs can contribute to the level of constitutive expression of H60a in tumor cell lines. We conclude that in 129/Sv strain mice, H60a can be regulated by its 3′UTR through IFNγ and unknown microRNAs. Since H60a mediates NK cell target recognition, our studies identify a cis element that can regulate virus and tumor surveillance.
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