化学诱导的相位过渡和染色质的全球形状重组
Tengfei Wang1, Shuxiang Shi1,2, Yuanyuan Shi3,4
1School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Nature communications
|September 9, 2023
概括
抗癌药物阿德里亚米 (Adriamycin) 通过诱导相位分离,导致染色质凝结. 这种机制影响细胞中的染色质相互作用,可访问性和基因表达.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生化学
- 基因组学就是基因组学.
背景情况:
- 化学物质可以在细胞内的相分离生物分子凝聚物中积聚.
- 染色体,DNA和蛋白质的复合体,经历相分离.
- 了解与染色素的药物相互作用对于癌症治疗至关重要.
研究的目的:
- 使用超分辨率成像,识别诱导染色体相变的化学物质.
- 为了研究阿德里亚米对染色体结构和功能的影响.
主要方法:
- 超高分辨率显微镜用于选化学品.
- Hi-C和ATAC-seq用于对染色体相互作用和可访问性的定量分析.
- 在体外实验中研究药物与激素相互作用的实验.
主要成果:
- 阿德里亚米辛 (doxorubicin) 在各种细胞类型中诱导局部染色体凝聚和全球形状变化.
- 亚德里亚米的染色质凝聚减弱了拓相关领域内的相互作用.
- 阿德里亚米辛会导致A/B区间的切换,降低染色质的可访问性,并改变转录组形状.
- 阿德里亚米辛复合体与素H1结合,诱导其相位过渡,并在体外形成纤维聚合物.
结论:
- 阿德里亚米辛利用相分离驱动的机制来改变染色质结构.
- 这项研究揭示了一种广泛使用的化疗药物的新型作用机制.
- 阶段分离是阿德里亚米与染色素相互作用的一个关键过程.
相关概念视频
Nucleosome Remodeling
9.2K
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...
9.2K
Duplication of Chromatin Structure
5.6K
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
5.6K
Heterochromatin
13.9K
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...
13.9K
Chromatin Modification in iPS Cells
1.7K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
1.7K
Spreading of Chromatin Modifications
8.3K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.3K
Chromatin Packaging
15.5K
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
15.5K


