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相关概念视频

Transcription Factors02:16

Transcription Factors

76.7K
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...
76.7K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

6.5K
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...
6.5K
General Transcription Factors01:30

General Transcription Factors

5.5K
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...
5.5K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

9.4K
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...
9.4K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

7.5K
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...
7.5K
Master Transcription Regulators02:23

Master Transcription Regulators

7.0K
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...
7.0K

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相关实验视频

Updated: Sep 9, 2025

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
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High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

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多重重叠的结合点决定了转录因子占用率

Shubham Khetan1, Brent S Carroll1, Martha L Bulyk2,3

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Nature
|September 3, 2025
PubMed
概括
此摘要是机器生成的。

我们开发了PADIT-seq以发现新的,低亲和度的转录因子 (TF) 的DNA结合点. 这揭示了重叠的结合点如何集体控制基因表达,并影响人类的特征和疾病.

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Identifying Transcription Factor Olig2 Genomic Binding Sites in Acutely Purified PDGFRα+ Cells by Low-cell Chromatin Immunoprecipitation Sequencing Analysis
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相关实验视频

Last Updated: Sep 9, 2025

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
06:38

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

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Identifying Transcription Factor Olig2 Genomic Binding Sites in Acutely Purified PDGFRα+ Cells by Low-cell Chromatin Immunoprecipitation Sequencing Analysis
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科学领域:

  • 基因组学
  • 分子生物学
  • 生物信息学

背景情况:

  • 转录因子 (TF) 通过特定序列的DNA相互作用来调节基因表达.
  • 现有的高吞吐量方法难以识别低亲缘关系的TF结合位点,这对基因调节至关重要.
  • 低 afinity 位点越来越多地被认可为它们在精确的时空基因表达控制中的作用.

研究的目的:

  • 开发一种用于全面测定TF DNA结合偏好的新方法.
  • 确定以前未被检测到的低亲缘关系TF结合点.
  • 提出TF结合的新模型及其在基因调节和疾病中的作用.

主要方法:

  • 通过体外转录和RNA测序 (PADIT-seq) 来开发蛋白与DNA的亲和力.
  • 在所有十个基对DNA序列中对六个TF的结合偏好的综合测定.
  • 分析TF结合点重叠及其对基因组占用率的影响.

主要成果:

  • PADIT-seq成功检测了数百个新的,低亲和度的TFsDNA结合点.
  • 在高亲和度位点旁边的核酸会形成重叠的低亲和度位点,在体内调节TF结合.
  • 一个基于多重重叠站点的TF绑定模型被提出.

结论:

  • TF结合是由多个重叠结合位点的集体效应决定的,而不仅仅是单个高亲和度位点.
  • 重叠绑定模型解释了TF的竞争和相似TF的区别绑定场所使用情况.
  • 该模型重新定义了非编码变体的影响,展示了它们如何改变多个部位以影响基因表达,人类特征和疾病.