癌症中的基因组基因的RNA聚合酶II超转录FFPE样本FFPE样本
Steven Henikoff1,2, Ye Zheng1,3, Ronald M Paranal3
1Basic Science Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|April 1, 2024
概括
全基因组超转录,即RNA聚合酶II (RNAPII) 活性升高,在癌症中很常见. 这项研究将基因组基因的RNAPII升高与癌症过度扩散和动体积积症联系起来,为精确瘤学提供了洞察力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 全基因组超转录在人类癌症中普遍存在,并且与预后不佳有关.
- 了解驱动癌症超转录的机制对于开发有效疗法至关重要.
研究的目的:
- 用一种新的FFPE-CUTAC方法研究RNA聚合酶II (RNAPII) 在癌症进展中的作用.
- 确定与各种癌症类型的超转录相关的特定基因组区域和基因.
主要方法:
- 应用FFPE-CUTAC方法用于在甲固定嵌 (FFPE) 组织段中全基因组映射RNAPII.
- 对小鼠质瘤和人类瘤,包括脑膜瘤和乳腺癌中的RNAPII占用率的分析.
- RNAPII水平与瘤等级,复发和染色体异常的相关性.
主要成果:
- 从小型临床样本中证明了小鼠质瘤和人类瘤的全球RNAPII升高.
- 确定了与HER2放大和选择性扫描相关的区域RNAPII升高.
- 发现基因组基因的RNAPII占用与脑膜瘤WHO等级相关,预测了复发,并与染色体损失相对应.
- 在各种乳腺癌中观察到 histone 基因的 RNAPII 升高.
结论:
- 由升高的RNAPII驱动的基因超转录可能会限制S相进展的速度,促进癌症过度扩散和动质积分.
- 研究结果表明,基因组基因超转录是癌症发展和进展的重要驱动因素.
- 这项研究对精密瘤学具有广泛的影响,突出了潜在的治疗点.
相关概念视频
RNA Polymerase II Accessory Proteins
9.2K
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...
9.2K
Epigenetic Regulation
3.0K
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...
3.0K
Eukaryotic RNA Polymerases
24.2K
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
24.2K
Transcription Elongation Factors
10.8K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
10.8K
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
Transcription Initiation
16.4K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
16.4K


