通过肌细胞增强因子-2的转录共抑制剂Cabin1的特定序列招募
Aidong Han1, Fan Pan, James C Stroud
1Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Nature
|April 18, 2003
概括
肌细胞增强因子-2 (MEF2) 转录因子招募像Cabin1.1这样的共同抑制剂. 这项研究揭示了MEF2B与Cabin1和DNA结合的晶体结构,阐明了转录抑制的关键机制.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 是一个遗传学.
背景情况:
- 肌细胞增强因子-2 (MEF2) 转录因子调节T细胞,神经元和肌肉细胞.
- MEF2通过协同激活剂/协同抑制剂调解依赖的转录抑制和激活.
- MEF2介导的转录抑制与心肌细胞缩有关.
研究的目的:
- 阐明转录共抑制剂MEF2招募的分子机制.
- 为了确定MEF2B,Cabin1和DNA之间的相互作用的结构基础.
主要方法:
- MEF2B MADS-box/MEF2S 域与 Cabin1 图案和 DNA 结合的 X 射线晶体学.
- 在2.2A分辨率下对三元复合结构的分析.
主要成果:
- 确定了MEF2B MADS-box/MEF2S域,Cabin1图案和DNA的晶体结构.
- 机1形成了一个两形阿尔法螺旋,在MEF2S域上结合了一个疏水槽.
- 在三元复合体中观察到三螺旋相互作用.
结论:
- 晶体结构显示了一个稳定的MEF2S域与MADS盒的相互作用.
- 证明了MEF2向DNA招募共抑制剂Cabin1和II类HDAC的一般机制.
- 这一发现为MEF2介导的转录调节提供了洞察力.
更多相关视频
相关概念视频
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...
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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...
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...
RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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...


