主转录因子决定了细胞类型对TGF-β信号传递的特定反应
Alan C Mullen1, David A Orlando, Jamie J Newman
1Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Cell
|November 1, 2011
概括
主转录因子如Oct4,Myod1和PU.1决定Smad3结合的地方,控制细胞对转化生长因子β (TGF-β) 信号的特定反应.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 转化增长因子β (TGF-β) 信号传递对于各种细胞功能至关重要.
- 转录因子Smad2和Smad3 (Smad2/3) 调解TGF-β信号传递.
- 根据细胞类型,TGF-β信号引发不同的细胞反应.
研究的目的:
- 调查Smad2/3如何实现细胞类型特定的基因组占用.
- 确定主转录因子在指导Smad3结合中的作用.
- 了解细胞特异性TGF-β反应背后的机制.
主要方法:
- 在不同细胞类型 (胚胎干细胞,肌管,亲B细胞) 中对Smad3的全基因组占用率分析.
- 测试以确定对Smad3结合的主转录因子的要求.
- 对TGF-β对由主转录因子结合的基因的信号效应的分析.
- 在非肌肉细胞中实验诱导主转录因子 (Myod1).
主要成果:
- Smad3与特定于细胞类型的主转录因子共占基因组:ESC中的Oct4,肌管中的Myod1和亲B细胞中的PU.1.
- 主转录因子对于Smad3基因组结合至关重要.
- TGF-β信号主要影响这些主转录因子占据的基因.
- 在非肌肉细胞中诱导Myod1将Smad3结合重定向到与Myod1相关的部位.
结论:
- 特定于细胞类型的主转录因子决定了Smad2/3.3的基因组标.
- 这些主因子是细胞特异性TGF-β信号输出结果的关键协调者.
- 这种机制解释了保存的信号通路如何产生多样化的细胞反应.
相关概念视频
General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...

