通过蛋白质控制基因表达,这些蛋白质通过相同的域将许多替代核酸结构结合在一起
1Discovery, InsideOutBio, Charlestown, MA 02129, USA.
International journal of molecular sciences
|January 10, 2026
概括
替代核酸结构 (ANS) 在基因组中动态形成. 计算建模表明转录因子结合这些结构,可能增强基因调节. 这揭示了ANS在生物过程中的新角色.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 结构生物学 结构生物学
背景情况:
- 替代核酸结构 (ANS),包括Z-DNA,三倍体,G-四倍体和i-动机,在历史上被驳回,因为缺乏生物相关性的证据.
- 已知转录因子 (TFs) 结合了正规的B-DNA,对它们与ANS的相互作用的理解有限.
- ANS是由特定的重复序列称为flipons动态形成的,特别丰富在促进器区域.
研究的目的:
- 通过先进的计算建模,研究已知的B-DNA结合TFs与替代核酸结构 (ANS) 的潜在结合.
- 探索ANS在基因转录调节和TF相互作用中的作用.
- 阐明TF与ANS相互作用的机制,以及这如何影响基因组扫描和促进体调节.
主要方法:
- 在优化条件下使用AlphaFold V3 (AF3) 的计算建模.
- 分析TF与各种ANS的对接相互作用,包括Z-DNA和G-四重复合体.
- 研究甲基氨酸修饰对TF结合Z-DNA的影响.
主要成果:
- 已知的B-DNA结合TFs,包括HLH和bZIP同质体,被证明可以与ZNA和GQ等ANS接.
- 甲基氨酸的修改促进了HLH和bZIP同型分子与Z-DNA的结合.
- 观察到异构体只与预先形成的Z-DNA结合,这表明它在TF复合体组装中的作用.
结论:
- 与ANS的TF相互作用可能会增强在活跃基因中的相关B-DNA位点的基因组扫描.
- 与Z-DNA对接可能有助于TF异构体的组装和稳定,从而快速发现促进子调节的最佳组合.
- 这项研究强调了一种新的基因调节机制,涉及动态ANS及其与转录因子的相互作用.
相关概念视频
Cooperative Binding of Transcription Regulators
7.1K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.1K
Cooperative Binding of Transcription Regulators
2.4K
2.4K
Regulation of Expression Occurs at Multiple Steps
25.7K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
25.7K
Regulation of Expression Occurs at Multiple Steps
3.9K
3.9K
Chromatin Structure Regulates pre-mRNA Processing
8.1K
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...
8.1K
Structure of a Gene
15.4K
A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
15.4K


