人类细胞巨型病毒感染会利用染色体组织来降低TEAD1转录因子活性
Khund Sayeed1, Sreeja Parameswaran1, Matthew J Beucler2
1Center for Autoimmune Genomics and Etiology, Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
bioRxiv : the preprint server for biology
|April 22, 2024
概括
人类细胞巨乳病毒 (HCMV) 感染改变了染色质可访问性和TEAD1转录因子活性. 这会影响发育途径,特别是眼睛和耳朵的发育.
科学领域:
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 发展生物学 发展生物学
背景情况:
- 人类细胞巨乳病毒 (HCMV) 是一种广泛传播的疹病毒,感染全球80%的人口.
- 冠状病毒感染与发育缺陷有关,特别是在感官器官.
研究的目的:
- 研究HCMV感染对人类染色质可访问性,循环和相关信号通路的影响.
- 阐明TEAD1转录因子在HCMV诱导的表观遗传和发育变化的作用.
主要方法:
- 在HCMV感染后48小时内对染色质可访问性和循环的全基因组分析.
- 对转录因子结合,基因组修饰 (H3K27ac) 和基因表达的综合分析.
- 对Hippo信号通路组件的评估,包括TEAD1和YAP1.
主要成果:
- HCMV感染引发了染色质可访问性和循环的广泛变化,影响了数十万个基因组区域.
- 观察到TEAD1转录因子活性显著降低,影响Hippo的信号传输.
- 在感染后发生了TEAD1结合,H3K27ac标记和染色体循环相互作用的协和损失.
- 已经确定了四种不同的机制,用于HCMV诱导的TEAD1活动的减少.
- 改变的TEAD1机制在与眼睛和耳朵发育相关的遗传位置上得到了丰富.
结论:
- 型冠状病毒感染严重扰乱染色质结构和TEAD1介导的转录调节.
- TEAD1 作为 HCMV 破坏的发育途径的中央调节者.
- 这些发现提供了对HCMV在先天性眼睛和耳朵异常中的作用的机制性见解.
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
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
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...
6.9K
Duplication of Chromatin Structure
5.5K
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
5.5K
Chromatin Position Affects Gene Expression
23.3K
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...
23.3K
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K


