NKX2.2的主要β细胞特异性功能通过NK2特异性域进行介导
Vladimir Abarinov1,2, Joshua A Levine1, Angela J Churchill1
1Department of Genetics and Development, Columbia University, New York, New York 10032, USA.
Genes & development
|June 26, 2023
概括
NKX2.2 特定域 (SD) 对于胰腺β细胞功能和胰岛素生产至关重要,但对于中枢神经系统发育至关重要. 这揭示了一个转录因子如何控制不同的细胞系统.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录因子 (TFs) 调节细胞命运承诺的基因表达.
- 对复杂的遗传网络进行TF控制的机制尚未完全理解,特别是对多种细胞类型中的TF.
- NKX2.2 是一种涉及各种发育过程的TF.
研究的目的:
- 研究NKX2.2特定域 (SD) 在β细胞功能和中枢神经系统发育中的作用.
- 阐明NKX2.2实现组织特异性基因调节的机制.
- 了解单一的TF如何指导不同的转录程序.
主要方法:
- 局部定向突变发生以突变NKX2.2 SD.
- 在突变模型中分析β细胞的发育和功能.
- 在中枢神经系统中评估NKX2.2-依赖细胞类型的发展.
- 对NKX2.2-调节转录的基因表达分析.
主要成果:
- NKX2.2 SD的突变影响了β细胞前体的发育和胰岛素的表达,导致新生儿糖尿病.
- NKX2.2 SD对成年β细胞功能至关重要,通过染色体重塑剂和核孔复合相互作用调节关键转录.
- 在中枢神经系统中,NKX2.2 SD对于NKX2.2-依赖细胞类型的发展是不可或缺的.
- NKX2.2在胰腺和神经上皮层中指导不同的转录程序.
结论:
- NKX2.2 SD是beta细胞特异性功能的关键决定因素.
- NKX2.2利用其SD调节不同组织中的不同调节作用.
- 这项研究揭示了通过单一TF对组织特异性基因调节的一种新机制.
更多相关视频
05:24Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia
Published on: February 21, 2021
4.2K
11:27A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
9.2K
相关概念视频
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
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.3K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
Insulin and C-peptide are...
1.3K
Adrenergic Receptors: β Subtype
1.8K
β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors...
1.8K
General Transcription Factors
5.4K
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...
5.4K
Insulin Secretory Vesicles
5.0K
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
5.0K
