缺陷的基因素遗传促进了瘤的进展
Congcong Tian1, Jiaqi Zhou1, Xinran Li1
1CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
Nature communications
|June 10, 2023
概括
对表观遗传记忆至关重要的父母组织蛋白的遗传受损,可以推动癌症的进展. 这项研究表明,缺陷的组素沉积如何重编程细胞,促进瘤生长和转移.
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
- 癌症生物学 癌症生物学
背景情况:
- 忠实地继承父母组织蛋白质对于维持表观遗传信息和细胞身份至关重要.
- 父母组织激素沉积到复制DNA上取决于DNA化酶的MCM2子单元.
- 在人类疾病,特别是癌症中,异常的亲基质子分裂的作用仍然在很大程度上未被探索.
研究的目的:
- 为了研究受损的组织蛋白遗传对癌症进展的影响.
- 在乳腺癌细胞中使用MCM2-2A突变来建模缺陷的亲基因组激素结合.
- 了解改变的组质子遗传如何影响表观遗传景观和癌症中的基因表达.
主要方法:
- 在MCF-7乳腺癌细胞中引入了一个MCM2-2A突变 (受损的亲基因组激素结合).
- 在后代细胞中分析基因组修饰景观,重点是H3K27me3.
- 评估与发育,增殖和上皮细胞转变为介质细胞相关的基因表达变化.
- 修改细胞的正位素植入以评估瘤生长和体内转移.
主要成果:
- 缺陷的基因组遗传导致了基因组修饰场景的重新编程,特别是减少了压制性的H3K27me3标记.
- 降低的H3K27me3水平导致了参与发育,细胞增殖和上皮细胞转移到介质细胞的基因的抑制.
- 这些表观遗传变化赋予了健身优势,促进了瘤生长和在 ортотоп植入后的转移.
结论:
- 父母组织蛋白的遗传损伤可以显著推动瘤的进展.
- 异常的基因组沉积有助于表观遗传重编程,影响癌细胞表型.
- 这种机制突出显示了一种新的途径,该途径将组织素遗传与癌症的发展和扩散联系起来.
更多相关视频
08:12Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
Published on: May 5, 2022
4.0K
10:41An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
10.5K
相关概念视频
01:12Loss of Tumor Suppressor Gene Functions
4.9K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
01:37Epigenetic 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
03:17Inheritance 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
02:25Spreading 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
02:07Tumor Progression
6.4K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K