综合空间基因组学揭示了单个核的全球架构
Yodai Takei1, Jina Yun1, Shiwei Zheng2,3
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Nature
|January 28, 2021
概括
研究人员在单个小鼠细胞中绘制了数千个染色体位置,核结构和基因表达. 他们发现了核组织中的固定点, 并确定了可遗传的染色体标记,
科学领域:
- 细胞生物学
- 基因组学
- 表观遗传学
背景情况:
- 了解染色体结构,核组织和基因表达之间的关系至关重要.
- 单个细胞的高变异性需要在同一细胞内绘制多种模式.
研究的目的:
- 在单个小鼠胚胎干细胞中空间绘制染色体位置,染色质状态,核体和RNA表达.
- 确定核组织中的固定点及其与染色体标记和基因表达的关联.
- 调查染色体标记的遗传性,并确定不同的细胞亚群.
主要方法:
- 使用DNAseqFISH+对单个小鼠胚胎干细胞中的3660个染色体位点进行成像.
- 使用顺序免疫光测绘17种染色体标记和亚核结构.
- 在同一个细胞内评估了70种RNA的表达特征.
主要成果:
- 识别了许多"固定点",总是与特定的免疫光标记相关.
- 观察到高度表达的基因预定在活跃的核区,不论基因表达爆发.
- 发现了以特定的组合性染色体状态为特征的不同小鼠ES细胞亚群.
- 证明某些染色体标记 (H3K27me3,mH2A1) 在3-4代内是可遗传的,而其他标记则迅速波动.
结论:
- 基于seqFISH+的空间多模式方法为探索核组织和细胞状态提供了强大的工具.
- 固定的点和基因的预定位置表明结构化的核组织影响基因表达.
- 染色体标记的遗传性突出显示了细胞身份和变异性的表观遗传机制.
相关概念视频
The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to 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.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
DNA Microarrays
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to 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.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
The Nucleosome
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...
The Nucleosome Core Particle
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...


