在EZH2中核细胞相互作用表面的不可分割的RNA结合和染色质修饰活动
Emma H Gail1, Evan Healy1, Sarena F Flanigan1
1Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Nature genetics
|May 14, 2024
概括
聚合物抑制复合物2 (PRC2) 使用其RNA结合表面进行基因素甲基化,但不使用RNA结合本身. 这种与核细胞DNA的相互作用对于细胞中染色质修饰和基因抑制至关重要.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 基因规则 基因规则
背景情况:
- 多镇压复合体2 (PRC2) 对于在分化细胞中维持转录程序至关重要.
- 已知PRC2和RNA之间的相互作用,但其在PRC2功能中的调节作用仍然不清楚.
- PRC2的正规功能包括染色质修饰,特别是基因素甲基化.
研究的目的:
- 研究RNA结合在PRC2的染色质修饰和基因抑制活动中的作用.
- 要确定RNA结合本身或RNA结合表面的其他功能是否调节PRC2.2.
- 阐明RNA结合影响PRC2酶活性的机制.
主要方法:
- 利用了EZH2的功能分离突变,这是PRC2.2的催化子单元.
- 被测试的突变体在RNA结合方面有缺陷,但保留了甲基转移酶活性.
- 进行了体外和细胞内测试,以评估染色质修饰和基因抑制活动.
主要成果:
- 在EZH2RNA结合表面上需要一个特定的区域进行染色质修饰,独立于RNA结合.
- 这个表面与核细胞DNA相互作用,在体外和细胞中调解染色质的修饰.
- 一个缺陷RNA结合的突变体显示出正常的染色质修饰和基因抑制在血统承诺的细胞中.
结论:
- EZH2的RNA结合表面,而不是本身的RNA结合,对于基因素甲基化至关重要.
- 通过EZH2RNA结合表面与核细胞DNA的相互作用对于染色质修饰至关重要.
- 维持转录程序中的PRC2的功能是由它与染色质的相互作用调节的,独立于直接的RNA相互作用.
相关概念视频
Nucleosome Remodeling
9.1K
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...
9.1K
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
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
The Nucleosome Core Particle
909
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...
909
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
Euchromatin
6.9K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
6.9K


