H3K36甲基化通过调节相反的血统程序来维持细胞身份.
Michael S Hoetker1,2,3,4,5,6, Masaki Yagi1,2,3,4,5,6, Bruno Di Stefano1,2,3,4,5,6
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
Nature cell biology
|July 17, 2023
概括
基因组H3K36甲基化对于维持细胞身份至关重要. 用H3K36M突变减小这个标记会产生塑性细胞状态,使纤维细胞能够通过重新连接增强剂来变得多能.
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.
- 发育生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 维持细胞分化的表观遗传机制尚未完全理解.
- 基因突变在调节基因表达和细胞身份方面起着关键作用.
研究的目的:
- 研究H3K36甲基化在维持细胞身份中的作用.
- 探索改变H3K36甲基化如何影响细胞可塑性和多能诱导.
主要方法:
- 使用基因组突变物,特别是H3K36M,以耗尽H3K36甲基化.
- 检查了对TGFβ信号的细胞反应.
- 分析了使用Tet依赖机制的增强剂活性和转录因子重定向 (Sox2).
主要成果:
- H3K36M突变导致塑性纤维细胞状态,准备获得多能性.
- 通过降低TGFβ敏感度,H3K36M赋予了上皮的可塑性.
- 在分子层面上,H3K36M分解介质酶增强剂,并以Tet依赖的方式激活上皮质/干细胞增强剂,重定向Sox2.2.
结论:
- H3K36甲基化在维持细胞身份方面具有双重作用:维持细胞类型特定的程序和反对替代血统程序.
- 向H3K36甲基化提供了一种用于诱导细胞可塑性和多能性的新策略.
相关概念视频
Lineage Commitment
3.0K
Commitment is the process whereby stem cells:
3.0K
Inheritance of Chromatin Structures
6.3K
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...
6.3K
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
Epigenetic Regulation
3.1K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.1K
Histone Modification
13.4K
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...
13.4K
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


