在小鼠胚胎干细胞的转录调节中,Tet1的双重功能
Hao Wu1, Ana C D'Alessio, Shinsuke Ito
1Department of Molecular & Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California 90095, USA.
Nature
|April 1, 2011
概括
十一转位1 (Tet1) 蛋白调节小鼠胚胎干细胞中的DNA甲基化. Tet1促进多能性因子的表达,并通过招募PRC2.2来抑制发育基因.
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.
- 基因组学就是基因组学.
- 发育生物学 发展生物学
背景情况:
- 基因组甲基化 (5-甲基) 对于基因组调节和细胞身份至关重要.
- 十-十一转位 (Tet) 蛋白质将5-甲基细胞因转化为5-基甲基细胞因,这表明它在不同的表观遗传状态中发挥了作用.
- Tet1对于维持小鼠胚胎干细胞 (ES) 是必不可少的.
研究的目的:
- 研究Tet1在小鼠ES细胞表观遗传修饰和基因调节中的作用.
- 确定Tet1结合点及其对DNA甲基化的影响.
- 阐明Tet1在基因表达中的双重功能.
主要方法:
- 在小鼠ES细胞中,染色质免疫沉与高通量DNA测序 (ChIP-seq) 相结合.
- 对基因促进体的CpG丰富序列的Tet1结合的分析.
- 在Tet1耗尽后评估DNA甲基化水平和基因表达.
主要成果:
- Tet1优先结合活跃基因和Polycomb抑制基因的CpG丰富促进体.
- Tet1 枯竭会改变结合部位的 DNA 甲基化,但并非所有点都被下调.
- 通过Tet1介导的低甲基化维持多能性基因表达.
- 泰特1促进聚合体抑制复合体2 (PRC2) 招募用于发育基因抑制.
结论:
- 在ES细胞表观遗传调节中,Tet1发挥着双重作用.
- Tet1通过低甲基化促进多能性因子的转录.
- 通过招募PRC2.2,Tet1有助于镇压发展监管机构.
更多相关视频
15:13Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
10.7K
11:53An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C
Published on: June 1, 2018
6.1K
相关概念视频
02:16Transcription Factors
70.6K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
70.6K
02:36RNA Polymerase II Accessory Proteins
8.9K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
8.9K
02:33Combinatorial Gene Control
8.6K
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
8.6K
02:23Master Transcription Regulators
6.1K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.1K
01:30General Transcription Factors
5.9K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.9K
01:14Maintenance of the ES Cell State
1.9K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
1.9K