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相关概念视频

Transcription Factors02:16

Transcription Factors

75.7K
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...
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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.4K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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...
9.1K
Master Transcription Regulators02:23

Master Transcription Regulators

6.9K
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...
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Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

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Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
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相关实验视频

Updated: Jun 13, 2025

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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对于调节转录因子DNA结合选择性的pH动态的作用.

Kyle P Kisor1, Diego Garrido Ruiz2, Matthew P Jacobson2

  • 1Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, United States.

Nucleic acids research
|June 4, 2025
PubMed
概括

细胞内pH通过调节转录因子DNA结合直接影响基因表达. 在转录因子中保存的histidine作为pH传感器,改变DNA结合活性.

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 遗传学 是一个

背景情况:

  • 细胞内pH (pHi) 动态调节细胞中的关键过程,如增殖和分化.
  • 通过转录因子活性直接控制基因表达的pHi的作用仍未得到充分探索.
  • 感应pH的蛋白质中的histidine残留物是pHi依赖细胞功能的关键媒介.

研究的目的:

  • 调查转录因子是否可以作为pH传感器,直接调节基因表达.
  • 为了测试转录因子DNA结合域 (DBDs) 中的histidine残留物调节pH调节的DNA结合的假设.
  • 探索pHi动态对转录因子结合特异性和细胞行为的影响.

主要方法:

  • 通过指数式丰富的连接体的系统演化,然后进行测序 (SELEX-seq),以确定依赖pH的DNA结合动机.
  • 电泳运动转移试验 (EMSAs) 证实pH调节的结合亲缘关系.
  • 染色体免疫沉测序 (ChIP-seq) 和RNA测序 (RNA-seq) 用于分析全基因组结合和基因表达变化.
  • 位点定向的突变发生,以评估特定的胺残留物的作用.

主要成果:

  • 对FOX家族转录因子 (例如,FOXC2,FOXM1,FOXN1) 进行pH依赖的DNA结合动机偏好.

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相关实验视频

Last Updated: Jun 13, 2025

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  • 证明了FOXC2,FOXM1和FOXN1与特定基因的结合亲和力会因pHi的变化 (pH 7.0与7.5) 而显著改变.
  • 证明FOXC2的pH依赖活性是由其DBD中保存的histidine (His122) 介导的.
  • ChIP-seq和RNA-seq揭示了FOXC2促进体丰富和基因表达的pH依赖差异.
  • 结论:

    • 转录因子在其DBD中含有histidine残留物可以作为直接pH传感器,表现出pH调节的DNA结合选择性.
    • pHi动态可以直接调节转录因子活性,影响基因表达和细胞行为.
    • 这种机制与多个家族的超过85个转录因子相关,突出显示了细胞生物学中的基本调节途径.