H3K4me3 调节了RNA聚合酶II促进剂的近位暂停释放
Hua Wang1,2, Zheng Fan3,4,5, Pavel V Shliaha6
1Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|March 1, 2023
概括
通过控制RNA聚合酶II的暂停和延长而不是启动来调节基因表达. 这一发现澄清了H3K4me3在转录输出中的作用.
科学领域:
- 表观遗传学
- 分子生物学
- 基因调控
背景情况:
- 基因组H3 lysine 4三甲基化 (H3K4me3) 与转录起点有关.
- 由于复杂的SET1/COMPASS甲基转移酶作用,H3K4me3在转录中的确切功能尚不清楚.
研究的目的:
- 使用小鼠胚胎干细胞研究H3K4me3在转录调节中的特定作用.
- 要确定H3K4me3是否调节转录启动,延长或两者.
主要方法:
- 在小鼠胚胎干细胞中急性切除SET1/COMPASS复杂子单元.
- 分析H3K4甲基化状态 (H3K4me1,H3K4me2,H3K4me3) 和它们的周转率.
- 对转录输出,RNA聚合酶II (RNAPII) 暂停和延长动态的评估.
- 研究KDM5脱甲基酶在H3K4me3的转化中的作用.
- 检查集成组合子单位11 (INTS11) 的招聘情况.
主要成果:
- 在SET1/COMPASS复合物消去时完全失去H3K4甲基化.
- H3K4me3表现出比H3K4me1/H3K4me2更快的周转率,并且依赖KDM5脱甲基酶.
- H3K4me3的损失没有影响转录启动,但转录输出减少.
- 在没有H3K4me3的情况下,观察到RNAPII暂停的增加和延长的减缓.
- 对于INTS11的招募,H3K4me3是必不可少的,它促进了暂停的RNAPII驱逐和延长.
结论:
- H3K4me3在转录暂停释放和延长中发挥着关键作用.
- H3K4me3的主要功能是通过促进延长促进转录输出,而不是启动转录.
更多相关视频
10:49A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers
Published on: September 26, 2019
5.7K
10:09Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
Published on: January 26, 2018
7.6K
相关概念视频
RNA Polymerase II Accessory Proteins
9.3K
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...
9.3K
Chromatin Structure Regulates pre-mRNA Processing
7.1K
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...
7.1K
Transcription Initiation
16.5K
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...
16.5K
Eukaryotic RNA Polymerases
24.4K
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...
24.4K
The Eukaryotic Promoter Region
16.5K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
16.5K
Transcription Elongation Factors
11.0K
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...
11.0K
