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首页> 外文期刊>Molecular and Cellular Biology >DGCR14 Induces Il17a Gene Expression through the RORγ/BAZ1B/RSKS2 Complex
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DGCR14 Induces Il17a Gene Expression through the RORγ/BAZ1B/RSKS2 Complex

机译:DGCR14通过RORγ/ BAZ1B / RSKS2复合体诱导Il17a基因表达

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The Dgcr14/Es2 gene is located in a chromosomal region the loss of which has been associated with DiGeorge syndrome, a cause of immunodeficiency, heart defects, and skeletal abnormalities. However, the role of DGCR14 protein remains to be elucidated. Here, I found that DGCR14 protein acts as a coactivator of RORγt in TH17 cells. Biochemical purification of the RORγ coregulator complex allowed me to identify the associated DGCR14 protein by matrix-assisted laser desorption ionization–time of flight mass spectrometry. Overexpression of Dgcr14 mRNA enhanced RORγt-mediated transcriptional activity and facilitated TH17 cell differentiation. Furthermore, knockdown of Dgcr14 reduced Il17a mRNA expression. I also found that DGCR14 associated with ribosomal S6 kinase 2 (RSK2, also called RpS6ka3) and BAZ1B, both of which were recruited to the Il17a promoter during TH17 cell differentiation. Knockdown of Baz1b or RpS6ka3 also reduced Il17a mRNA expression, and Baz1b knockdown increased transcriptional suppressive histone marks (histone H3K9me3) on the Il17a promoter. My findings showed the roles of DGCR14, RSK2, and BAZ1B in the transcriptional regulation of Il17a mRNA during TH17 cell differentiation.
机译: Dgcr14 / Es2 基因位于染色体区域,该区域的丢失与DiGeorge综合征有关,后者是免疫缺陷,心脏缺陷和骨骼异常的原因。但是,DGCR14蛋白的作用尚待阐明。在这里,我发现DGCR14蛋白在T H 17细胞中作为RORγt的共激活因子。 RORγ调节剂复合物的生化纯化使我能够通过基质辅助激光解吸电离-飞行时间质谱法鉴定相关的DGCR14蛋白。 Dgcr14 mRNA的过表达增强RORγt介导的转录活性并促进T H 17细胞分化。此外,敲除Dgcr14减少 Il17a mRNA表达。我还发现DGCR14与核糖体S6激酶2(RSK2,也称为RpS6ka3)和BAZ1B相关,在T H 17细胞分化过程中,两者均被募集到 Il17a 启动子。敲除 Baz1b RpS6ka3 也会降低 Il17a mRNA表达,而 Baz1b 敲除会增加转录抑制组蛋白标记(组蛋白H3K9me3 )在 Il17a 启动子上。我的发现显示了在T H 17细胞分化过程中DGCR14,RSK2和BAZ1B在 Il17a mRNA转录调控中的作用。

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