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相关概念视频

General Transcription Factors01:30

General Transcription Factors

5.2K
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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Transcription Factors02:16

Transcription Factors

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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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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...
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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

9.8K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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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...
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Master Transcription Regulators02:23

Master Transcription Regulators

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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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相关实验视频

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HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
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人类序列特异性转录因子的位置依赖功能

Sascha H Duttke1, Carlos Guzman2, Max Chang2

  • 1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. sascha.duttke@wsu.edu.

Nature
|July 17, 2024
PubMed
概括

相对于转录起点 (TSS),转录因子 (TF) 结合位的位置决定了基因调控. 这种位置依赖解释了类似的TF结合位如何产生多样化的基因表达模式并导致疾病.

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Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
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Real-time Analysis of Transcription Factor Binding, Transcription, Translation, and Turnover to Display Global Events During Cellular Activation
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科学领域:

  • 基因组学和分子生物学
  • 基因调控和转录

背景情况:

  • 像促进剂和增强剂这样的监管元素含有转录因子 (TF) 的结合位.
  • 了解这些部位如何编码基因表达对于基因调节和疾病研究至关重要.
  • 类似的TF结合位安排可以导致不同的基因表达结果.

研究的目的:

  • 研究TF结合位相对于转录开始位 (TSS) 在基因调节中的作用.
  • 确定TF结合点的空间配置如何影响转录启动.
  • 阐明DNA序列变异导致转录变异和疾病的机制.

主要方法:

  • 从单个TSS的角度分析基因调节.
  • 使用了自然遗传变异,内源性TF蛋白水平的扰乱,以及大量并行报告测试.
  • 分析了与TSS相对的TF结合点发生情况,以确定位置偏好.

主要成果:

  • 证明了TF对转录启动的影响取决于位置.
  • 确定了几个与TSS相比高度优惠的TF绑定动机.
  • 显示TFs可以根据它们与TSS的精确位置激活或抑制转录启动.

结论:

  • TF结合点的位置和间距共同指导转录启动点和频率.
  • 揭示了相似的TF结合位数如何根据空间配置产生不同的基因调节结果.
  • 突出了TSS数据在解码基因组调控信息和了解疾病机制方面的关键作用.