人类叉转录因子中的误解变异揭示了叉DNA双特异性的决定因素
Jessica King1, Stephen S Gisselbrecht1, Julie-Alexia Dias2
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Cell reports
|October 22, 2025
概括
研究人员发现了非DNA接触的残留物,这些残留物决定了叉 (FH) 转录因子 (TF) 是否结合一个或两个DNA基因. 这一发现促进了对TF特异性和基因调节演变的理解.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- 转录因子 (TFs) 通过识别特定的DNA序列来调节基因表达.
- 叉头 (FH) TFs通常结合FKH或FHL动机,但有些结合两者,这是一个未知调节机制的现象.
研究的目的:
- 确定控制FH转录因子是否表现出单特异性或双特异性DNA结合活性的机制.
- 研究特定氨基酸残留在确定TF结合偏好的作用.
主要方法:
- 使用通用10-mer蛋白结合微阵列对12个参考FH蛋白,61个自然变异和22个设计突变的选.
- 对DNA结合活性进行分析,以确定特定序列的相互作用.
主要成果:
- 非接触DNA的氨基酸残留被确定为FH TF单特异性与双特异性的关键决定因素.
- 这表明,没有直接参与DNA结合的残留物可以在全质上影响动机识别.
结论:
- 非DNA接触残留物的变化可以将FH TFs在结合单个动机和结合多个动机之间切换.
- 这些发现对理解TF进化,人类特征以及基因调节网络的复杂性有影响.
相关概念视频
General Transcription Factors
6.7K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.7K
Transcription Factors
82.2K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.2K
Conserved Binding Sites
5.0K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.0K
Restarting Stalled Replication Forks
6.3K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.3K
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


