The Th1 cell regulatory circuitry is largely conserved between human and mouse.
The Th1 cell regulatory circuitry is largely conserved between human and mouse.
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DOI：
10.26508/lsa.202101075
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发表时间：
2021-11
影响因子：
4.4
通讯作者：
Jenner RG
中科院分区：
文献类型：
--
作者：
Henderson S;Pullabhatla V;Hertweck A;de Rinaldis E;Herrero J;Lord GM;Jenner RG
对人类和小鼠Th1谱系特定的转录因子T-bet的结合位点进行比较，发现结合位点存在差异，但大多数目标基因是共同的。由谱系决定转录因子控制的基因表达程序在物种之间通常是保守的。然而，传染病已经施加了巨大的进化压力，因此由免疫特异性转录因子调控的基因可能会显示出更大的差异。T-bet(Tbx21)是T辅助细胞I型(Th1)免疫的免疫特异性、谱系特异性转录因子，是细胞内病原体免疫应答的基础，也是炎症性疾病的基础。我们比较了小鼠和人类CD4+T细胞的T-bet基因组靶点，并将T-bet结合模式与物种特异性基因表达相关联。值得注意的是，我们发现大多数T-bet靶基因在小鼠和人类之间是保守的，要么是通过保留结合位点，要么是通过与转座子连接的插入相关的替代结合位点。物种特异性T-bet结合与转录因子结合基序和相关基因的物种特异性表达的差异有关。这些结果提供了Th1基因调控的全基因组跨物种比较，从而能够更准确地将炎症和传染病以及癌症的临床前模型中的遗传靶点和治疗方法转化为人类临床试验。
Comparison of the binding sites of the Th1 lineage-specifying transcription factor T-bet between human and mouse reveals differences in binding sites but that the most of the target genes are shared. Gene expression programs controlled by lineage-determining transcription factors are often conserved between species. However, infectious diseases have exerted profound evolutionary pressure, and therefore the genes regulated by immune-specific transcription factors might be expected to exhibit greater divergence. T-bet (Tbx21) is the immune-specific, lineage-specifying transcription factor for T helper type I (Th1) immunity, which is fundamental for the immune response to intracellular pathogens but also underlies inflammatory diseases. We compared T-bet genomic targets between mouse and human CD4+ T cells and correlated T-bet binding patterns with species-specific gene expression. Remarkably, we found that the majority of T-bet target genes are conserved between mouse and human, either via preservation of binding sites or via alternative binding sites associated with transposon-linked insertion. Species-specific T-bet binding was associated with differences in transcription factor–binding motifs and species-specific expression of associated genes. These results provide a genome-wide cross-species comparison of Th1 gene regulation that will enable more accurate translation of genetic targets and therapeutics from pre-clinical models of inflammatory and infectious diseases and cancer into human clinical trials.
DOI：
10.4049/jimmunol.0900519
发表时间：
2009-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shi G;Ramaswamy M;Vistica BP;Cox CA;Tan C;Wawrousek EF;Siegel RM;Gery I
通讯作者：
Gery I