与DNA复制和转录相结合的基因组伴侣控制分离的染色质元素,以维持细胞命运
Reuben Franklin1,2,3, Brian Zhang1,2,3, Jonah Frazier1,2,3
1Department of Biochemistry, University of California Riverside, Riverside, California 92521, USA.
Genes & development
|April 16, 2025
概括
像SPT6和CAF-1这样的基因组伴侣通过影响DNA复制和转录来调节细胞命运. 它们的独特机制突出显示了染色质组合途径如何控制干细胞自我更新和分化.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
背景情况:
- 对复制和转录等DNA模板过程来说,基因组陪伴者至关重要.
- 这些蛋白质在核细胞组合和维护染色体结构方面发挥作用.
- 新出现的证据表明,胰岛素伴侣也可能作为细胞命运的调节者.
研究的目的:
- 为了调查不同的基因素陪伴路径是否控制细胞命运.
- 为了确定这些通路是否通过相关机制发挥作用.
- 评估各种组织组织素伴侣在造血干细胞和祖细胞自我更新中的作用.
主要方法:
- 进行了一项查,以评估血液造血干细胞自我更新中的基因组伴侣蛋白需求.
- 一个同源的双诱导系统被生成,以扰乱DNA复制合 (CAF-1) 和转录合 (SPT6) 基因组伴侣通路.
- 在SPT6和CAF-1的干扰后,分析了细胞周期进展,染色质可访问性和血统选择.
主要成果:
- 所有经过测试的基因组辅导体都需要在不同程度上维持细胞命运.
- 失去了SPT6,一个转录合的伴侣,最强烈地促进了细胞分化.
- 干扰SPT6和CAF-1需要细胞分裂来诱导分化,但对细胞周期,染色质可访问性和基因表达有明显的影响.
结论:
- 基因组伴侣SPT6和CAF-1通过不同的机制维持干细胞命运.
- SPT6损失导致细胞循环停止和谱系特异化,受AP-1因素的影响.
- CAF-1的耗尽导致S相积累,并在异色彩区域改变了染色质的可访问性.
- 不同的染色体组合途径为操纵细胞命运提供了不同的策略.
相关概念视频
Duplication of Chromatin Structure
5.2K
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...
5.2K
Spreading of Chromatin Modifications
8.1K
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...
8.1K
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
Chromatin Modification in iPS Cells
1.6K
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...
1.6K
Nucleosome Remodeling
8.8K
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...
8.8K
Chromosome Replication
8.6K
Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins. This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
8.6K


