The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations.
The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations.
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DOI：
10.1182/blood-2013-02-486944
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发表时间：
2014-04
期刊：
影响因子：
20.3
通讯作者：
Christian Schmidl;L. Hansmann;T. Lassmann;Piotr J. Balwierz;H. Kawaji;M. Itoh;J. Kawai;Sayaka Nagao-Sato;Harukazu Suzuki;R. Andreesen;Y. Hayashizaki;A. Forrest;Piero Carninci;P. Hoffmann;M. Edinger;M. Rehli
中科院分区：
文献类型：
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作者：
Christian Schmidl;L. Hansmann;T. Lassmann;Piotr J. Balwierz;H. Kawaji;M. Itoh;J. Kawai;Sayaka Nagao-Sato;Harukazu Suzuki;R. Andreesen;Y. Hayashizaki;A. Forrest;Piero Carninci;P. Hoffmann;M. Edinger;M. Rehli
CD4(+)CD25(+)FOXP3(+)人类调节性T细胞(Tregs)对于自身耐受和免疫动态平衡是必不可少的。在这里，我们描述了CD4(+)CD25(高)CD45RA(+)幼稚和CD4(+)CD25(高)CD45RA(-)记忆树以及它们的CD25(-)传统T细胞(Tconv)体外扩增前后的启动子组。我们进行了全面的数字比较基因表达分析，发现了新的转录起始点，其中几个被确认为已知基因的替代启动子。对于所有体外扩展的亚集，我们另外生成了由组蛋白H3赖氨酸4单甲基化和组蛋白H3赖氨酸27乙酰化标记的稳定和活性增强子元件的全球图谱，描述了它们的细胞类型特异性基序特征，并评估了候选转录因子STAT5、FOXP3、RUNX1和ETS1在Treg和Tconv特异性增强子结构中的作用。基因表达数据的网络分析揭示了其他有助于细胞类型特异性的候选转录因子，以及由FOXP3相互作用伙伴和靶点主导的Tregs转录因子网络。总之，我们为人类Treg和Tconv亚群的基因表达和基因调控提供了一个全面且容易获得的资源。
CD4(+)CD25(+)FOXP3(+) human regulatory T cells (Tregs) are essential for self-tolerance and immune homeostasis. Here, we describe the promoterome of CD4(+)CD25(high)CD45RA(+) naïve and CD4(+)CD25(high)CD45RA(-) memory Tregs and their CD25(-) conventional T-cell (Tconv) counterparts both before and after in vitro expansion by cap analysis of gene expression (CAGE) adapted to single-molecule sequencing (HeliScopeCAGE). We performed comprehensive comparative digital gene expression analyses and revealed novel transcription start sites, of which several were validated as alternative promoters of known genes. For all in vitro expanded subsets, we additionally generated global maps of poised and active enhancer elements marked by histone H3 lysine 4 monomethylation and histone H3 lysine 27 acetylation, describe their cell type-specific motif signatures, and evaluate the role of candidate transcription factors STAT5, FOXP3, RUNX1, and ETS1 in both Treg- and Tconv-specific enhancer architectures. Network analyses of gene expression data revealed additional candidate transcription factors contributing to cell type specificity and a transcription factor network in Tregs that is dominated by FOXP3 interaction partners and targets. In summary, we provide a comprehensive and easily accessible resource of gene expression and gene regulation in human Treg and Tconv subpopulations.