miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.
miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.
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DOI：
10.1016/j.immuni.2014.03.014
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发表时间：
2014-06-19
期刊：
影响因子：
32.4
通讯作者：
Muljo, Stefan A.
中科院分区：
文献类型：
--
作者：
Escobar, Thelma M.;Kanellopoulou, Chrysi;Kugler, David G.;Kilaru, Gokhul;Nguyen, Cuong K.;Nagarajan, Vijayaraj;Bhairavabhotla, Ravikiran K.;Northrup, Daniel;Zahr, Rami;Burr, Patrick;Liu, Xiuhuai;Zhao, Keji;Sher, Alan;Jankovic, Dragana;Zhu, Jinfang;Muljo, Stefan A.
辅助性T - 17 （Th17）细胞谱系的描述需要一组定义良好的转录因子，但这些转录因子如何与转录后和表观遗传程序结合以调节基因表达尚不清楚。在体外和体内，我们发现mir -155缺陷CD4+ T细胞中Th17细胞细胞因子表达缺陷。Mir155与Th17细胞转录因子结合，在Th17细胞分化过程中高表达。mir -155缺陷- th17和-T调节（Treg）细胞表达Jarid2的量增加，Jarid2是一种dna结合蛋白，可将多梳抑制复合体2 （PRC2）招募到染色质上。在mir -155缺陷细胞中，PRC2结合染色质和H3K27组蛋白甲基化增加，与Il22、Il10、Il9和Atf3表达失败相一致。在Mir155缺失的情况下，Th17细胞细胞因子表达缺陷和Treg细胞稳态可以被Jarid2缺失部分抑制。因此，miR-155通过抑制Jarid2的抑制作用来促进Th17细胞的功能。
Specification of the T helper 17 (Th17) cell lineage requires a well defined set of transcription factors, but how these integrate with post-transcriptional and epigenetic programs to regulate gene expression is poorly understood. Here we found defective Th17 cell cytokine expression in miR-155-deficient CD4+ T cells in vitro and in vivo. Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient-Th17 and -T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9 and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.
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DOI：
10.1084/jem.20061692
发表时间：
2006-10-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cobb BS;Hertweck A;Smith J;O'Connor E;Graf D;Cook T;Smale ST;Sakaguchi S;Livesey FJ;Fisher AG;Merkenschlager M
通讯作者：
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DOI：
10.4049/jimmunol.1003049
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Goswami R;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
50.3
作者：
Abdel-Wahab O;Adli M;LaFave LM;Gao J;Hricik T;Shih AH;Pandey S;Patel JP;Chung YR;Koche R;Perna F;Zhao X;Taylor JE;Park CY;Carroll M;Melnick A;Nimer SD;Jaffe JD;Aifantis I;Bernstein BE;Levine RL
通讯作者：
Levine RL
DOI：
10.1126/science.1218004
发表时间：
2012-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Dudakov JA;Hanash AM;Jenq RR;Young LF;Ghosh A;Singer NV;West ML;Smith OM;Holland AM;Tsai JJ;Boyd RL;van den Brink MR
通讯作者：
van den Brink MR
影响因子：
6.4
作者：
Liesenfeld, O
通讯作者：
Liesenfeld, O