对HNF4生物学的结构性见解
Brice Beinsteiner1,2,3,4, Isabelle M L Billas1,2,3,4, Dino Moras1,2,3,4
1Laboratory IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre for Integrative Biology (CBI), Illkirch, France.
Frontiers in endocrinology
|July 5, 2023
概括
肝细胞核因子4 (HNF4) 是调节肝脏基因的关键转录因子. 本文审查了HNF4结构,疾病联系以及突变和修改如何影响其功能.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 遗传学 遗传学 是一个
背景情况:
- 肝细胞核因子4 (HNF4) 是核受体 (NR) 家族中的关键转录因子 (TF).
- 它在肝脏特异性基因表达中起着至关重要的作用,特别是在脂质和葡萄糖代谢中,对于发育至关重要.
- HNF4失调与I型糖尿病 (MODY1) 和血友病等疾病有关.
研究的目的:
- 审查HNF4.4的DNA结合域 (DBD) 和连接体结合域 (LBD) 的结构.
- 将HNF4结构与其他核受体进行比较.
- 从结构角度讨论HNF4α生物学,重点关注突变和翻译后修改.
主要方法:
- 孤立的HNF4DNA结合域 (DBD) 和连接体结合域 (LBD) 的结构分析.
- 将HNF4结构与其他核受体进行比较.
- 对HNF4α突变和翻译后修饰的现有文献的审查.
主要成果:
- 详细比较HNF4 DBD和LBD结构与其他NRs.
- 了解病理突变如何影响HNF4的结构和功能.
- 了解翻译后修改对HNF4α受体活性的影响.
结论:
- 对HNF4的结构洞察力对于理解其监管作用至关重要.
- 病理突变和翻译后修改显著影响HNF4结构功能关系.
- 本综述提供了关于HNF4生物学及其与疾病相关性的结构性视角.
相关概念视频
Histone Modification
13.4K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.4K
The Nucleosome Core Particle
954
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
954
Co-activators and Co-repressors
7.4K
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...
7.4K
Heterochromatin
14.0K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
14.0K
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
Inheritance of Chromatin Structures
6.3K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K


