Reciprocal regulation of RORγt acetylation and function by p300 and HDAC1.
Reciprocal regulation of RORγt acetylation and function by p300 and HDAC1.
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p300 和 HDAC1 对 ROR gamma t 乙酰化和功能的相互调节
DOI：
10.1038/srep16355
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发表时间：
2015-11-09
影响因子：
4.6
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Wu Q;Nie J;Gao Y;Xu P;Sun Q;Yang J;Han L;Chen Z;Wang X;Lv L;Tsun A;Shen J;Li B
辅助性T细胞17（Th 17）不仅在保护免受细菌和真菌感染方面发挥关键作用，而且还参与自身免疫性疾病的发病机制。视黄酸相关孤儿受体（RORγt）是通过直接转录激活白细胞介素17（A）（IL-17）参与Th 17细胞分化的关键转录因子。RORγt本身是如何调节的尚不清楚。本文报道了具有组蛋白乙酰转移酶（HAT）活性的p300与RORγt的K81残基相互作用并使其乙酰化。敲低p300可下调Th 17细胞中RORγt蛋白和RORγ t介导的基因表达。此外，p300还能促进RORγ t介导的转录激活。有趣的是，组蛋白去乙酰化酶（HDAC）HDAC 1也可以与RORγt相互作用并降低其乙酰化水平。总之，我们的数据揭示了RORγt的翻译后调节，揭示了组蛋白乙酰转移酶p300和组蛋白去乙酰化酶HDAC 1 β调节RORγ t介导的IL-17转录激活的潜在机制。
T helper 17 (Th17) cells not only play critical roles in protecting against bacterial and fungal infections but are also involved in the pathogenesis of autoimmune diseases. The retinoic acid-related orphan receptor (RORγt) is a key transcription factor involved in Th17 cell differentiation through direct transcriptional activation of interleukin 17(A) (IL-17). How RORγt itself is regulated remains unclear. Here, we report that p300, which has histone acetyltransferase (HAT) activity, interacts with and acetylates RORγt at its K81 residue. Knockdown of p300 downregulates RORγt protein and RORγt-mediated gene expression in Th17 cells. In addition, p300 can promote RORγt-mediated transcriptional activation. Interestingly, the histone deacetylase (HDAC) HDAC1 can also interact with RORγt and reduce its acetylation level. In summary, our data reveal previously unappreciated posttranslational regulation of RORγt, uncovering the underlying mechanism by which the histone acetyltransferase p300 and the histone deacetylase HDAC1 reciprocally regulate the RORγt-mediated transcriptional activation of IL-17.