NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression.
NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression.
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DOI：
10.4049/jimmunol.1103160
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Kobayashi KS
中科院分区：
文献类型：
--
作者：
Meissner TB;Liu YJ;Lee KH;Li A;Biswas A;van Eggermond MC;van den Elsen PJ;Kobayashi KS
严格调控MHC-I类基因的表达对CD8T细胞活化和宿主获得性免疫反应至关重要。MHC-I类基因的启动子含有一个保守的核心模块，即W/S-X-Y基序，它组装了一个核蛋白复合体，称为MHC-增强体。NLRC5是NLR(核苷酸结合域，富含亮氨酸重复序列)蛋白家族的成员，是新发现的MHC I类基因的转录调控因子。NLRC5结合并反式激活MHC-I类基因的近端启动子，尽管反式激活的分子机制尚不清楚。在这里，我们证明了NLRC5介导的MHC I类基因的诱导需要W/S和X1，X2顺式调控元件。转录因子RFX5、RFXAP和RFXANK/B组成RFX蛋白复合体，与X1-box结合，与NLRC5协同表达MHC I类分子。免疫共沉淀实验表明，NLRC5通过其锚定蛋白重复序列与RFX亚单位RFXANK/B特异地相互作用。此外，我们还发现NLRC5可以与具有组蛋白乙酰转移酶活性的转录共激活子CBP/p300和GCN5以及atf1协同工作。综上所述，我们的数据表明NLRC5参与了MHC I类特异的增强体，该增强体组装在MHC I类近端启动子保守的W/S-X-Y核心模块上，包括RFX因子成分和CREB/ATF1家族转录因子，以促进MHC I类基因的表达。
Tight regulation of MHC class I gene expression is critical for CD8 T cell activation and host adaptive immune responses. The promoters of MHC class I genes contain a well-conserved core module, the W/S-X-Y motif, which assembles a nucleoprotein complex termed MHC-enhanceosome. A member of the NLR (nucleotide binding domain, leucin-rich repeat) protein family, NLRC5, is a newly identified transcriptional regulator of MHC class I genes. NLRC5 associates with and transactivates the proximal promoters of MHC class I genes, although the molecular mechanism of transactivation has not been understood. Here, we show that NLRC5-mediated MHC class I gene induction requires the W/S and X1, X2 cis-regulatory elements. The transcription factors RFX5, RFXAP and RFXANK/B, which compose the RFX protein complex and associate with the X1-box, cooperate with NLRC5 for MHC class I expression. Co-immunoprecipitation experiments revealed that NLRC5 specifically interacts with the RFX subunit RFXANK/B via its ankyrin repeats. In addition, we show that NLRC5 can cooperate with ATF1 and the transcriptional co-activators CBP/p300 and GCN5, which display histone acetyltransferase activity. Taken together, our data suggest that NLRC5 participates in an MHC class I specific enhanceosome, which assembles on the conserved W/S-X-Y core module of the MHC class I proximal promoters, including the RFX factor components and CREB/ATF1 family transcription factors to promote MHC class I gene expression.
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