PHF2调节了神经发生过程中的sarcomeric基因转录
Taku Fukushima1, Yuka Hasegawa2, Sachi Kuse2
1Department of Physiology, School of Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
PloS one
|May 3, 2024
概括
酶PHF2通过去甲基化素H3 lysine 9 dimethyl (H3K9me2) 来调节骨肌肉的发育. PHF2淘汰会损害对肌肉纤维形成至关重要的sarcomeric基因表达.
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
- 肌肉的发展 肌肉的发展
背景情况:
- 肌肉发育,骨肌肉形成的过程,主要由肌肉发育调节因子 (MRF) 控制.
- 表观遗传修饰显著影响MRF转录,但它们在肌细胞形成中的具体作用尚不清楚.
- 众所周知,PHF2是一种表观基因组修饰酶,可以去甲基化素3 lysine 9 dimethyl (H3K9me2).
研究的目的:
- 为了研究表观基因组修饰酶PHF2在肌细胞形成中的作用.
- 阐明PHF2通过H3K9me2脱甲基化调节骨肌肉基因表达的机制.
主要方法:
- 利用CRISPR/Cas9产生Phf2淘汰赛 (KO) C2C12神经细胞.
- 进行RNA测序以分析Phf2KO细胞分化后的全球转录变化.
- 进行基因本体学 (GO) 分析以确定受影响的生物通路.
主要成果:
- 证实了phf2mRNA表达和PHF2蛋白在肌细胞和肌管中的定位.
- Phf2 KO显著损害了参与骨肌肉纤维形成和发育的基因的表达.
- 关键的sarcomeric基因 (例如,Myhs,Mybpc2) 的表达在Phf2KO细胞中减少,在特定的sarcomeric和肌肉发育基因 (Mybpc2,Mef2c,Myh7) 上观察到增加的H3K9me2修饰.
结论:
- PHF2在肌肉发育过程中对基因表达的调节起着至关重要的作用.
- 通过PHF2介导的H3K9me2脱甲基化对于萨尔科默基因的正确表达至关重要.
- 这些发现突出了PHF2作为骨肌肉发育中的关键表观遗传调节剂.
相关概念视频
Master 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
Formation of Muscle Fibers from Myoblasts
4.9K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
4.9K
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
The Sarcomere
8.0K
A sarcomere is a microscopic segment repeating in a myofibril. The sarcomere fundamentally consists of two main myofilaments: thick filaments called myosin and thin filaments called actin. These filaments interact by sliding past each other in response to stimulus. In addition to myosin and actin, several other proteins, such as tropomyosin, troponin, titin, nebulin, myomesin, α-actinin, and dystrophin, play crucial roles in regulating, structuring, and functioning of the sarcomere.
Each...
Each...
8.0K
General Transcription Factors
5.3K
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...
5.3K
Combinatorial Gene Control
8.3K
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...
8.3K


