SOX-5 activates a novel RORγt enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation.
SOX-5 activates a novel RORγt enhancer to facilitate experimental autoimmune encephalomyelitis by promoting Th17 cell differentiation.
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SOX-5 激活一种新型 RORγt 增强剂，通过促进 Th17 细胞分化促进实验性自身免疫性脑脊髓炎
DOI：
10.1038/s41467-020-20786-w
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发表时间：
2021-01-20
影响因子：
16.6
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Tian Y;Han C;Wei Z;Dong H;Shen X;Cui Y;Fu X;Tian Z;Wang S;Zhou J;Yang D;Sun Y;Yuan J;Ni B;Wu Y
辅助性T细胞17型（Th 17）在炎症和自身免疫性疾病的发病机制中具有重要功能。类维生素A相关孤儿受体-γt（RORγt）是Th 17细胞分化和功能所必需的。然而，RORγt表达的转录调控，特别是在增强子水平，仍然知之甚少。我们在Th 17细胞中发现了一种新的RORγt基因增强子RORCE 2。RORCE 2缺陷抑制RORγt表达和Th 17分化，导致实验性自身免疫性脑脊髓炎严重程度降低在Th 17细胞中，RORCE 2通过SRY盒转录因子5（SOX-5）与RORγt启动子成环，并且RORCE中SOX-5结合位点的缺失废除了RORCE 2功能并影响信号转导和转录激活因子3（STAT 3）与RORγt基因座的结合。总之，我们的数据突出了调节Th 17分化和功能的分子机制，这可能代表了Th 17相关疾病的新干预线索。辅助性T细胞17（Th 17）是炎症性疾病和真菌感染保护的重要介质，受转录因子（TF）RORγt的重要调节。在这里，作者鉴定了一种新的RORγt增强子RORCE 2，它与另一种TF Sox 5协同作用，与RORγt启动子结合，从而调节RORγt表达。
T helper type 17 (Th17) cells have important functions in the pathogenesis of inflammatory and autoimmune diseases. Retinoid-related orphan receptor-γt (RORγt) is necessary for Th17 cell differentiation and functions. However, the transcriptional regulation of RORγt expression, especially at the enhancer level, is still poorly understood. Here we identify a novel enhancer of RORγt gene in Th17 cells, RORCE2. RORCE2 deficiency suppresses RORγt expression and Th17 differentiation, leading to reduced severity of experimental autoimmune encephalomyelitis. Mechanistically, RORCE2 is looped to RORγt promoter through SRY-box transcription factor 5 (SOX-5) in Th17 cells, and the loss of SOX-5 binding site in RORCE abolishes RORCE2 function and affects the binding of signal transducer and activator of transcription 3 (STAT3) to the RORγt locus. Taken together, our data highlight a molecular mechanism for the regulation of Th17 differentiation and functions, which may represent a new intervening clue for Th17-related diseases. T helper 17 (Th17) cells are important mediators of inflammatory diseases and fungal infection protection, and are critically regulated by the transcription factor (TF), RORγt. Here the authors identify a new enhancer for RORγt, RORCE2, which synergizes with another TF, Sox5, for binding with RORγt promoter and thereby modulation of RORγt expression.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
6.7
作者：
McClellan MJ;Wood CD;Ojeniyi O;Cooper TJ;Kanhere A;Arvey A;Webb HM;Palermo RD;Harth-Hertle ML;Kempkes B;Jenner RG;West MJ
通讯作者：
West MJ
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA