对于TFIID在多能转录电路中的中心作用
W W M Pim Pijnappel1, Daniel Esch, Marijke P A Baltissen
1Molecular Cancer Research, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.
Nature
|March 19, 2013
概括
一般转录因子TFIID对于保持胚胎干细胞的身份和重编程体细胞成为诱导多能干细胞至关重要. 提高TFIID水平显著提高了重新编程的效率.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 胚胎干细胞 (ES) 具有多能性,其特点是开放的染色质和高转录率,由Oct4,Sox2,Klf4,c-Myc (OSKM) 和Nanog.等核心因子维持.
- 强制表达OSKM因子可以将体细胞重新编程成诱导多能干细胞 (iPSC).
- 基底转录机制,如转录因子IID (TFIID) 综合体,在维持多能性和重编程方面的作用尚不清楚.
研究的目的:
- 研究TFIID复合体在维持ES细胞多能状态中的作用.
- 确定TFIID对体细胞转化为iPSCs的重编程的影响.
主要方法:
- 在小鼠ES细胞中对TFIID子单元的敲除.
- 评估TFIID淘汰对多能基因电路的影响.
- 评估纤维细胞重编程到iPSC的效率,有或没有TFIID操纵.
主要成果:
- TFIID knockdown 破坏ES细胞中的多能电路,并抑制体细胞重编程.
- TFIID子单元和OSKM因子形成一个前循环,对于多能细胞中稳定的转录至关重要.
- TFIID子单元的短暂表达显著提高了重新编程的效率.
结论:
- TFIID是转录因子介导的重编程的关键组成部分.
- 在重编程过程中,TFIID在建立和维护细胞身份方面发挥着至关重要的作用.
- 像TFIID这样的转录复合体有助于细胞可塑性,促进重新编程到各种细胞状态.
相关概念视频
01:30General 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...
02:16Transcription 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...
02:16Transcription 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...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
02:23Master 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...
02:23Master 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...