在转录因子异型中,分子相互作用和调节性质的广泛变化
Luke Lambourne1, Kaia Mattioli2, Clarissa Santoso3
1Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Molecular cell
|March 27, 2025
概括
大多数人体转录因子 (TF) 基因产生多种蛋白质异型,具有不同的功能. 这项研究表明,三分之二的替代TF异型表现出改变的分子活动,影响基因调节在分化和癌症.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物信息学是一种生物信息学.
背景情况:
- 人类转录因子 (TF) 基因通常编码多种蛋白质异型.
- 这些异构体产生的功能差异尚未完全理解.
- 这种异形多样性可能会增加基因调节网络的复杂性.
研究的目的:
- 系统地比较大量人类TF异型的分子活动.
- 为了研究替代TF异型的功能影响.
- 确定替代TF异型的类别和作用.
主要方法:
- 从246个TF基因中对693个异型进行了系统比较.
- 评估DNA结合,蛋白质结合,转录激活,亚细胞局部化和凝结物形成.
- 对异型特异性功能差异和分类的分析.
主要成果:
- 与参考异型相比,三分之二的替代TF异型表现出分子活动的差异.
- 功能差异通常是无法预测的,仅仅基于序列.
- 确定了两个主要类别",回线器"和"负调节器",它们与差异化和癌症有关.
结论:
- 替代性TF异型引入了显著的功能多样性.
- 同位体特异性表达和相互作用增加了基因调节网络的复杂性.
- 对于理解基因调节,分化和疾病至关重要的是TF功能的异形意识的表征.
相关概念视频
Transcription Factors
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...
Transcription Factors
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...
Cooperative Binding of Transcription Regulators
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 dimers that...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
General Transcription Factors
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...
Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...


