Master transcription factors determine cell-type-specific responses to TGF-β signaling.

Master transcription factors determine cell-type-specific responses to TGF-β signaling.
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DOI:
10.1016/j.cell.2011.08.050
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发表时间:
2011-10-28
期刊:
影响因子:
64.5
通讯作者:
Young RA
Young RA
中科院分区:
生物学1区
文献类型:
--
作者:
Mullen AC;Orlando DA;Newman JJ;Lovén J;Kumar RM;Bilodeau S;Reddy J;Guenther MG;DeKoter RP;Young RA

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通过转录因子Smad 2和Smad 3(Smad 2/3)介导的转化生长因子β(TGF-β)信号传导在不同细胞类型中指导不同的反应。在这里,我们报告说,Smad 3共同占据的基因组与细胞类型特异性主转录因子。因此,Smad 3与胚胎干细胞(ES)中的Oct 4、肌管中的Myod 1和pro-B细胞中的PU.1一起占据基因组。我们发现这些主转录因子是Smad 3占据所必需的,并且TGF-β信号在很大程度上影响了主转录因子结合的基因。此外,我们表明,诱导Myod 1在非肌肉细胞是足够的重新定向Smad 3 Myod 1网站。我们的结论是,细胞类型特异性的主转录因子决定了Smad 2/3结合的基因,因此负责协调TGF-β信号传导的细胞类型特异性作用。
Transforming growth factor beta (TGF-β) signaling, mediated through the transcription factors Smad2 and Smad3 (Smad2/3), directs different responses in different cell types. Here we report that Smad3 co-occupies the genome with cell-type-specific master transcription factors. Thus, Smad3 occupies the genome with Oct4 in embryonic stem (ES) cells, Myod1 in myotubes, and PU.1 in pro-B cells. We find that these master transcription factors are required for Smad3 occupancy and that TGF-β signaling largely affects the genes bound by the master transcription factors. Furthermore, we show that induction of Myod1 in non-muscle cells is sufficient to re-direct Smad3 to Myod1 sites. We conclude that cell-type-specific master transcription factors determine the genes bound by Smad2/3 and are thus responsible for orchestrating the cell-type-specific effects of TGF-β signaling.
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