KSHV TR删除事件揭示了基因调节中的增强剂-促进剂动态
Tomoki Inagaki1, Ashish Kumar1, Kang-Hsin Wang1
1Department of Dermatology, School of Medicine, the University of California Davis (UC Davis), Sacramento, California, United States of America.
PLoS pathogens
|December 4, 2025
概括
卡波西的肉瘤相关性疹病毒 (KSHV) 终端重复 (TR) 调节病毒基因表达. 减少TR拷贝数量会通过降低原蛋白含有蛋白4 (BRD4) 招募到病毒促进体而损害KSHV的活性.
科学领域:
- 病毒学 病毒学
- 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:
- 卡波西的肉瘤相关性疹病毒 (KSHV) 终端重复 (TR) 是可诱导的性基因促进者的已知增强剂.
- 含基因的蛋白4 (BRD4) 通过与转录机械相互作用,对基因增强至关重要.
- 在调节BRD4招募和病毒再激活方面,TR拷贝数的作用尚未完全理解.
研究的目的:
- 调查KSHV TR复制数减少对病毒基因表达和重新激活的影响.
- 阐明TR影响原蛋白含有蛋白4 (BRD4) 招募和功能的机制.
- 探索LANA核体和液体-液体相分离在KSHV转录调节中的作用.
主要方法:
- 产生具有减少TR副本数量的重组KSHV (TR5与TR21).
- 在感染细胞中评估病毒基因表达和重新激活效率.
- 对含原蛋白的蛋白4 (BRD4) 和对病毒染色质的LANA招募的分析.
- 使用纯化蛋白质和TR DNA片段,研究LANA-BRD4相互作用和液态液态相分离 (LLPS).
主要成果:
- 将KSHV TR拷贝数从21减少到5显著减弱病毒基因表达在de novo感染和受损的活性化期间.
- 降低TR拷贝数导致原体含有蛋白4 (BRD4) 减少对病毒基因促进者的招募,与受诱导的转录受损相关.
- 较大的LANA核体与增强的KSHV反激活有关,并且LANA被证实是 BRD4 潜伏色素占用的原因.
- 需要BRD4才能使LANA形成液-液相分离的点,TR DNA有助于更大的BRD4-LANALLPS,模仿细胞增强点.
结论:
- KSHV TR 长度和 LANA 结合为病毒发作建立了一个增强器域,调节 KSHV 溶性复制.
- 这种增强剂的强度受TR拷贝数和先前的转录记忆的影响,决定了KSHV重新激活的效率.
- 通过LANA介导的BRD4到TR含有染色质的招募对于建立增强器功能和促进KSHV光学复制至关重要.
相关概念视频
02:32Position-effect Variegation
7.0K
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
7.0K
01:37Epigenetic Regulation
3.7K
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...
3.7K
01:46Epigenetic Regulation
33.4K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
33.4K
01:32Chromatin Modification in iPS Cells
2.1K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.1K
02:25Spreading of Chromatin Modifications
9.3K
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...
9.3K
02:32Exon Recombination
4.1K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
4.1K