Tet2 调节胚胎干细胞中活性增强剂的 Sin3a 招募
Julio C Flores1,2,3, Simone Sidoli4, Meelad M Dawlaty1,2,3
1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA.
iScience
|July 17, 2023
概括
十-十一转位2 (Tet2) 通过DNA脱甲基化和与Sin3a.合作,调节胚胎干细胞 (ESC) 中的基因. Tet2 Tet2 Tet2 Tet2 Tet2 Tet2 Tet2 Tet2 Tet2 Tet2 Tet2
科学领域:
- 表观遗传学和基因调控
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- Tet2 是十一转位 (Tet) 家族中的一个关键酶,参与DNA脱甲基和基因调节.
- 它在胚胎干细胞 (ESC) 中的特定作用,包括催化和非催化功能,仍然不完全理解.
研究的目的:
- 阐明Tet2的催化和非催化功能在ESC中调节基因的不同作用.
- 确定Tet2的交互合作伙伴及其在监管区域的招聘机制.
主要方法:
- 利用Tet2催化突变和淘汰赛ESC来区分催化依赖和独立的功能.
- 采用ChIP-seq来识别Tet2目标基因,活性增强剂和促进剂.
- 研究了素脱乙酶Sin3a的招募及其与Tet2和Tet1.1的关系.
主要成果:
- 确定了由催化和非催化功能调节的Tet2基因,在活性增强剂和促进剂中进行Tet2丰富.
- 发现Sin3a是Tet2的合作伙伴,与Tet2在促进剂和活性增强剂上同定位.
- 证明,在活性增强剂中,Tet2 缺乏会降低 Sin3a 的占用,而 Tet1/Tet2 的联合损失 (但不是它们的催化活性) 会降低 Sin3a.
结论:
- Tet2的催化和非催化功能对于DNA脱甲基和Sin3a在ESC中的活性增强剂的招募至关重要.
- Tet2 在协调表观遗传修饰方面发挥着重要作用,通过与 Sin3a.等染色质修饰剂的相互作用来协调表观遗传修饰.
相关概念视频
02:36RNA Polymerase II Accessory Proteins
9.3K
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...
9.3K
02:23Master Transcription Regulators
6.9K
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...
6.9K
01:14Maintenance of the ES Cell State
2.2K
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...
2.2K
02:04Co-activators and Co-repressors
7.4K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.4K
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
02:35Transcription Elongation Factors
10.9K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
10.9K