ZBTB转录因子的聚合调节了染色质占用率
Paul M C Park1, Jiho Park2, Jared Brown3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Molecular cell
|July 12, 2024
概括
像BCL6这样的转录因子 (TF) 可以形成聚合物. 这项研究发现,18个ZBTB TFs也聚合,通过增强染色质结合和抑制基因来影响基因表达.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 结构生物学 结构生物学
背景情况:
- 宽复杂,电车轨道和bric-à-brac (BTB) 域是一个在许多转录因子 (TF) 中发现的蛋白质图案.
- BCL6是一种致癌性TF,通过其BTB域形成聚合物,由小分子稳定.
- 在BTB域架构中的相似性表明其他BTB蛋白也可能自我组装.
研究的目的:
- 研究人类BTB蛋白质中聚合的潜力.
- 描述由ZBTB TFs形成的更高阶结构.
- 了解ZBTB TF聚合物对基因调节的功能影响.
主要方法:
- 细胞光记者测定用于选189个人类BTB蛋白质的聚合.
- 生物化学分析和冷电子显微镜 (cryo-EM) 用于研究ZBTBTF结构.
- 分析了染色质占用率和基因表达,以评估功能影响.
主要成果:
- 18个ZBTBTF被确定为具有聚合能力.
- 生物化学和冷EM研究证实ZBTB TFs聚合成纤维.
- ZBTB TFs的BTB域介导聚合增加了聚类结合位的染色质占用率,导致基因抑制.
结论:
- ZBTB TFs可以形成更高级的聚合物结构.
- TF聚合在调节基因表达方面发挥着重要作用.
- 这项工作揭示了一种被低估的基因调节机制,涉及TF自我组装.
相关概念视频
Transcription Factors
75.8K
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...
75.8K
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
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Eukaryotic Transcription Activators
10.9K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
10.9K
Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
Master Transcription Regulators
6.9K
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...
6.9K


