人类4D核的结构和功能的综合视图
, Job Dekker1,2, Betul Akgol Oksuz1
1Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
bioRxiv : the preprint server for biology
|November 1, 2024
概括
4D核体项目绘制了人类基因组在干细胞和纤维细胞中的3D组织,揭示了复杂的染色质结构和相互作用. 这项工作将基因组折叠与基因功能和复制联系起来,有助于了解疾病变异.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 三维 (3D) 基因组组织,称为4D核,对于调节基因组功能至关重要.
- 了解这种空间结构是解读基因调节,DNA复制和细胞过程的关键.
研究的目的:
- 在人类胚胎干细胞 (H1-hESCs) 和纤维细胞 (HFFc6) 中全面地绘制和分析3D基因组组织.
- 整合多种基因组数据集,详细了解空间基因组架构及其功能影响.
- 开发用于预测基因组折叠和遗传变异影响的计算模型.
主要方法:
- 从4D核子项目中集成多个基因组数据集.
- 3D基因组映射试验的基准测试.
- 开发基因组结构和变异的3D计算模型.
- 分析染色体域,结构循环和促进剂-增强剂相互作用.
主要成果:
- 在H1-hESC和HFFc6.6中的多个尺度上的空间基因组特征的详细注释.
- 识别了超过十万个结构循环和促进器-增强器相互作用.
- 建立染色体折叠,核组织,基因转录和DNA复制之间的联系.
- 来自DNA序列的基因组折叠的计算预测的演示,突出显示遗传变异的潜在影响.
结论:
- 这项研究为人类3D基因组组织提供了丰富的,多原子的观点.
- 它增强了对基因组结构,功能和调节之间的复杂联系的理解.
- 这些发现提供了关于遗传变异如何影响基因组结构和功能的见解.
相关概念视频
The Nucleosome
1.3K
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
1.3K
Structural Organization of the Human Body: An Overview
13.5K
It is convenient to consider the body's structures in terms of fundamental levels of organization that increase in complexity: subatomic particles, atoms, molecules, organelles, cells, tissues, organs, organ systems, and organisms.
To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms, and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of...
To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms, and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of...
13.5K
Chromatin Packaging
16.6K
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
16.6K
The Nucleus
4.4K
The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression and precisely regulates the production of proteins within the cell. In contrast, the DNA inside the mitochondria and chloroplast only carries out functions that are specific to those organelles.
Arrangement of DNA within Nucleus
The regulation of gene expression inside the nucleus is dependent on many factors, including the DNA structure. The...
Arrangement of DNA within Nucleus
The regulation of gene expression inside the nucleus is dependent on many factors, including the DNA structure. The...
4.4K
Nucleic Acid Structure
6.0K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
DNA Structure
DNA...
6.0K
The Nucleosome Core Particle
880
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...
880


