由Slc29a3/Unc5b位点TAD边界干扰引起的转录变化的方向和模式取决于特定组织的表观遗传背景
Paul Salnikov1,2, Polina Belokopytova1,2, Alexandra Yan1,2
1Institute of Cytology and Genetics, Novosibirsk, Russia.
Epigenetics & chromatin
|August 12, 2025
概括
破坏广泛表达的基因之间的拓学关联域 (TAD) 边界导致组织特定的基因表达变化,而不是统一的激活或沉默. 这突出了TADs的重要性.
科学领域:
- 基因组学就是基因组学.
- 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:
- 拓关联域 (TADs) 通过调节调节元素之间的相互作用,对基因表达调节至关重要.
- 之前的研究集中在发育基因的TAD扰乱;这项研究研究了具有广泛表达特征的基因.
- 在小鼠中的Slc29a3 / Unc5b位点,包含在两个不同的TAD中无处不在表达的基因,被选择用于分析.
研究的目的:
- 调查TAD边界在调节无处不在表达基因的基因表达中的作用.
- 分析破坏两个TAD之间的CTCF边界对基因表达特征的影响.
- 为了评估TAD边界破坏后的组织特异性转录反应.
主要方法:
- 在小鼠Slc29a3/Unc5b位点的TAD边界的四个CTCF结合点的破坏.
- 分析局部染色体结构,包括先前存在的和新的长距离相互作用.
- 用UMI辅助的向RNA测序来评估各种器官中特定基因的转录变化.
主要成果:
- TAD边界破坏改变了染色质结构,废除了现有的循环,形成了新的长距离相互作用.
- 基因表达的变化在多个器官的规模和方向上是可变的和组织特异的.
- 目前的基因组架构和基因调节模型部分解释了观察到的转录变化.
结论:
- 在广泛表达的基因之间破坏绝缘体元素会导致适度的,上下文依赖的转录变化.
- TAD边界有助于特定环境的基因调节,即使在家庭环境中也是如此.
- 需要精细的模型来预测非编码结构变异对基因调节的影响.
更多相关视频
11:36Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
Published on: April 21, 2023
2.4K
10:28Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
6.5K
相关概念视频
02:35Chromatin Position Affects Gene Expression
23.7K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
23.7K
01:30General 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
02:16Transcription Factors
76.8K
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...
76.8K
01:37Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
02:41Chromatin Structure Regulates pre-mRNA Processing
7.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.2K
02:23Master 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