甲状腺受体α的激素反应元素包括特定的远端5'-侧翼DNA
David P Lohry1, Taylor A Stevens1, Tongye Shen1
1Department of Biochemistry and Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, USA.
Science advances
|November 27, 2024
概括
保存的DNA序列与甲状腺受体α (TRα) 相互作用,调节基因转录. 这些相互作用扭曲了DNA结构,挑战了当前对激素反应元素 (HREs) 的定义.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 基因转录依赖于转录因子和DNA之间的精确相互作用.
- 远端DNA序列在调节转录因子活性中的作用尚未完全理解.
研究的目的:
- 研究5'-侧翼DNA序列与甲状腺受体α (TRα) 之间的相互作用.
- 阐明这些相互作用控制转录活动的机制.
主要方法:
- 模拟建模和动力学的模拟.
- 染色体免疫沉降测序 (ChIP-seq) 是一种
- 原子力显微镜 (AFM) 的使用
- 记者基因测试试验
主要成果:
- 保存的5'-侧翼序列直接与TRα的内在无序的氨基末端区域相互作用.
- 确定了特定的lysine/arginine-DNA小沟相互作用,导致DNA结构扭曲.
- 记者基因分析证实了这些远端序列在转录调节中的重要性.
结论:
- 目前对DNA激素反应元素 (HREs) 的定义是不充分的.
- 未来的HRE描述应该包括保存的远端DNA序列.
- 核受体本质上有障碍的区域中的氨酸/氨酸丰富的基因对转录控制至关重要.
相关概念视频
Intracellular Hormone Receptors
54.8K
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
54.8K
Target Cell Response to Hormones
2.9K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
2.9K
Synthesis and Regulation of Thyroid Hormones
4.2K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
4.2K
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Functions of Thyroid Hormones
2.5K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
2.5K
The Eukaryotic Promoter Region
16.2K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
16.2K


