A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells

FuW.; ErgunA.; LuT.; HillJ.A.; HaxhinastoS.; FassettM.S.; GazitR.; AdoroS.; GlimcherL.; ChanS.; KastnerP.; RossiD.; CollinsJ.J.; MathisD.; BenoistC.

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A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells

机译：多重冗余遗传开关“锁定”调节性T细胞的转录特征

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The transcription factor Foxp3 participates dominantly in the specification and function of Foxp3 + CD4 + regulatory T cells (T reg cells) but is neither strictly necessary nor sufficient to determine the characteristic T reg cell signature. Here we used computational network inference and experimental testing to assess the contribution of other transcription factors to this. Enforced expression of Helios or Xbp1 elicited distinct signatures, but Eos, IRF4, Satb1, Lef1 and GATA-1 elicited exactly the same outcome, acting in synergy with Foxp3 to activate expression of most of the T reg cell signature, including key transcription factors, and enhancing occupancy by Foxp3 at its genomic targets. Conversely, the T reg cell signature was robust after inactivation of any single cofactor. A redundant genetic switch thus 'locked in' the T reg cell phenotype, a model that would account for several aspects of T reg cell physiology, differentiation and stability.

机译：转录因子Foxp3主要参与Foxp3 + CD4 +调节性T细胞（T reg细胞）的规格和功能，但对于确定特征性T reg细胞签名既非严格必要也不充分。在这里，我们使用计算网络推论和实验测试来评估其他转录因子对此的贡献。 Helios或Xbp1的强制表达引起了不同的特征，但是Eos，IRF4，Satb1，Lef1和GATA-1产生了完全相同的结果，与Foxp3协同作用，激活了大多数T reg细胞特征的表达，包括关键的转录因子，并提高Foxp3在其基因组目标上的占有率。相反，任何单个辅因子失活后，T reg细胞信号均很强健。因此，一个冗余的遗传开关“锁定”了T reg细胞的表型，该模型将解释T reg细胞的生理，分化和稳定性的几个方面。

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《Nature immunology》 |2012年第10期|共9页
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FuW.; ErgunA.; LuT.; HillJ.A.; HaxhinastoS.; FassettM.S.; GazitR.; AdoroS.; GlimcherL.; ChanS.; KastnerP.; RossiD.; CollinsJ.J.; MathisD.; BenoistC.;
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1. A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells [J] . FuW., ErgunA., LuT., Nature immunology . 2012,第10期

机译：多重冗余遗传开关“锁定”调节性T细胞的转录特征
2. Cis-regulatory signatures of orthologous stress-associated bZIP transcription factors from rice, sorghum and Arabidopsis based on phylogenetic footprints [J] . Fuyu Xu, Myoung-Ryoul Park, Ai Kitazumi, BMC Genomics . 2012,第1期

机译：基于系统发育足迹的稻，高粱和拟南芥直系同源胁迫相关bZIP转录因子的顺式调控特征
3. The p65 subunit of NF-kappa B is redundant with p50 during B cell proliferative responses, and is required for germline CH transcription and class switching to IgG3. [J] . Horwitz BH, Zelazowski P, Shen Y, The Journal of Immunology: Official Journal of the American Association of Immunologists . 1999,第4期

机译：NF-κB的p65亚基在B细胞增殖反应中与p50多余，是种系CH转录和类转换为IgG3所必需的。
4. Multi-Scale Genetics of Transcription Network: Understanding the Regulatory Roles of All 300 Transcription Factors from a Single Organism Escherichia coli [C] . Akira ISHIHAMA, Hiroshi OGASAWARA, Tomohiro SHIMADA, International Symposium on Micro-NanoMechatronics and Human Science . 2007

机译：转录网络的多尺度遗传学：了解来自单一有机体大肠杆菌的所有300种转录因子的调节作用
5. Testing the components of a genetic switch in living cells: In vivo dimerization dynamics of Cro Transcriptional Regulator [D] . Harris, Jacqueline Johnson 2010

机译：测试活细胞中遗传开关的组成：Cro转录调节剂的体内二聚化动力学
6. A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells [O] . Wenxian Fu, Ayla Ergun, Ting Lu, -1

机译：在调节性T细胞的转录签名甲多个冗余基因开关锁
7. A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells [O] . Wenxian Fu, Ayla Ergun, Ting Lu, 2012

机译：在“调节T细胞的转录签名”中乘法繁殖遗传开关锁定

A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells

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