Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.
Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.
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DOI：
10.1016/j.immuni.2018.04.024
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发表时间：
2018-06-19
期刊：
影响因子：
32.4
通讯作者：
Rothenberg EV
中科院分区：
文献类型：
--
作者：
Hosokawa H;Ungerbäck J;Wang X;Matsumoto M;Nakayama KI;Cohen SM;Tanaka T;Rothenberg EV
转录因子通常通过在与DNA结合的位点上的作用来调节基因表达。然而，转录因子介导的激活和抑制功能的平衡还不完全清楚。在这里，我们发现转录因子PU.1在早期T细胞发育过程中调节基因表达，通过将伙伴转录因子招募到其自身的结合位点，并在PU.1缺失时将它们从它们所偏好的结合位点耗尽。伴侣因子Satb1和Runx1的去除主要发生在PU.1本身不结合的位点。在模型细胞系系统和正常T细胞发育中，与伴侣因子“盗窃”位点相关的基因对于PU.1抑制的基因都是富集的，尽管缺乏结合。因此，系统级竞争性招募动态允许PU.1通过其自身的靶点和远距离作用影响基因表达。转录因子通过序列特异性DNA结合调控靶基因。当它们绑定在一起时，它们可能会协作，但在单独绑定时，它们被认为是独立的。Hosokawa， Ungerbäck等人表明，PU.1广泛地改变了Runx1 DNA结合的全基因组位点选择，使PU.1能够远距离抑制一些靶基因。
Transcription factors normally regulate gene expression through their action at sites where they bind to DNA. However, the balance of activating and repressive functions that a transcription factor can mediate is not completely understood. Here, we showed that the transcription factor PU.1 regulated gene expression in early T cell development both by recruiting partner transcription factors to its own binding sites and by depleting them from the binding sites that they preferred when PU.1 was absent. The removal of partner factors Satb1 and Runx1 occurred primarily from sites where PU.1 itself did not bind. Genes linked to sites of partner factor ‘theft’ were enriched for genes that PU.1 represses despite lack of binding, both in a model cell line system and in normal T cell development. Thus, system-level competitive recruitment dynamics permit PU.1 to affect gene expression both through its own target sites and through action at a distance. Transcription factors regulate target genes via sequence-specific DNA binding. They may collaborate when bound together, but are assumed to be independent at sites where they bind alone. Hosokawa, Ungerbäck et al. show that PU.1 broadly shifts the genome-wide site choice of Runx1 DNA binding, enabling PU.1 to repress some target genes at a distance.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0711961105
发表时间：
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影响因子：
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