The Th1 cell regulatory circuitry is largely conserved between human and mouse
The Th1 cell regulatory circuitry is largely conserved between human and mouse
复制标题
Th1 细胞调节电路在人类和小鼠之间很大程度上是保守的
DOI：
10.1101/2021.01.11.426266
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Henderson S
中科院分区：
文献类型：
--
作者：
Henderson S
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，感染性疾病已经施加了深刻的进化压力，因此由免疫特异性转录因子调控的基因可能会表现出更大的分歧。T-bet（Tbx 21）是辅助性T细胞I型（Th 1）免疫的免疫特异性、谱系特异性转录因子，其是对细胞内病原体的免疫应答的基础，但也是炎性疾病的基础。我们比较了小鼠和人CD 4 +T细胞之间的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靶基因在小鼠和人之间是保守的，通过保留结合位点或通过与转座子连接的插入相关的替代结合位点。种属特异性T-bet结合与转录因子结合基序的差异和相关基因的种属特异性表达相关。这些结果提供了Th 1基因调控的全基因组跨物种比较，这将使遗传靶点和治疗方法从炎症和感染性疾病和癌症的临床前模型更准确地转化为人类临床试验。
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.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
转录因子 T-bet 由多种途径诱导，并在 Th1 细胞反应期间阻止内源性 Th2 细胞程序。
影响因子：
32.4
作者：
Zhu J;Jankovic D;Oler AJ;Wei G;Sharma S;Hu G;Guo L;Yagi R;Yamane H;Punkosdy G;Feigenbaum L;Zhao K;Paul WE
通讯作者：
Paul WE
影响因子：
32.4
作者：
Nakayamada S;Kanno Y;Takahashi H;Jankovic D;Lu KT;Johnson TA;Sun HW;Vahedi G;Hakim O;Handon R;Schwartzberg PL;Hager GL;O'Shea JJ
通讯作者：
O'Shea JJ
影响因子：
32.4
作者：
Wei G;Abraham BJ;Yagi R;Jothi R;Cui K;Sharma S;Narlikar L;Northrup DL;Tang Q;Paul WE;Zhu J;Zhao K
通讯作者：
Zhao K
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK