发现蛋白质编码扰乱引起的染色质失调在尺度上
Max Frenkel1,2,3, Margaux L A Hujoel4,5,6, Zachary Morris7
1Cellular and Molecular Biology Graduate Program, University of Wisconsin, Madison, Wisconsin, USA.
bioRxiv : the preprint server for biology
|October 2, 2023
概括
我们开发了PROD-ATAC,这是一种研究遗传变异如何影响色素的新方法. 这种方法揭示了许多致癌性结体表现出开拓性活动,广泛影响基因调节.
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:
- 了解遗传变异的功能影响对于疾病研究至关重要.
- 目前的方法很难跟上变体发现的规模.
研究的目的:
- 引入PROD-ATAC,这是一种高通量方法,用于评估蛋白质编码变异对染色质可访问性的影响.
- 描述融合对染色质水平的影响.
主要方法:
- PROD-ATAC涉及在细胞系中表达聚合变体库.
- 用于测量变异效应的单细胞转移酶可访问染色质 (scATAC) 试验.
- 在100多个融合和对照中进行了表征.
主要成果:
- 开拓者活动是不同频率的融合的共同特征.
- 融合诱导的基因失调可能是无关背景的.
- 功能获取的开创性在合中很普遍.
- 在不同的融合中确定了融合机制.
结论:
- PROD-ATAC提供了融合诱导的染色体变化的全局视图.
- 在癌症中确定了共享的失调模式.
- PROD-ATAC可以适应各种不同的蛋白质编码变体集.
相关概念视频
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Epigenetic 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
Chromatin Position Affects Gene Expression
23.4K
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...
23.4K
Chromatin Structure Regulates pre-mRNA Processing
7.0K
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...
7.0K
Nucleosome Remodeling
9.2K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.2K
Heterochromatin
13.8K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
13.8K


