电子盒独立的染色质招募将MYOD转化为转录抑制剂
Chiara Nicoletti1, Jimmy Massenet1, Andreas P Pintado-Urbanc2,3
1Sanford Burnham Prebys Medical Discovery Institute, Development, Aging and Regeneration Program, La Jolla, CA.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
MYOD是一种基因调节剂,可以激活肌肉细胞的发育或抑制其他基因. 这种双重功能,涉及E-box依赖和独立的机制,揭示了细胞身份调节的新见解.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞重编程 细胞重编程
背景情况:
- MYOD被称为转录激活剂,对骨肌肉发育至关重要.
- 它在促进染色质可访问性和诱导肌体生成方面的作用已得到充分证实.
- 主流观点将MYOD的功能限制在转录激活上.
研究的目的:
- 识别MYOD除了其作为转录激活剂的作用之外的以前未被识别的特性.
- 调查MYOD的基因抑制机制及其对染色质可访问性的影响.
- 了解MYOD在细胞命运决定中的功能多功能性.
主要方法:
- 研究了MYOD的染色体结合,独立于E-box序列.
- 分析了MYOD对染色质可访问性和基因表达的影响.
- 检查了特定MYOD功能域在镇压中的作用.
- 评估了包括H3K27ac和H4 Kacme在内的基因组修饰,与MYOD介导的抑制有关.
主要成果:
- MYOD通过E-box独立的染色体结合作用作为基因表达的抑制剂,减少染色体的可访问性.
- 抑制机制包括促进体结合 (对于生长因子基因) 和远端调节元件退役 (对于血统基因),需要特定的MYOD域.
- 由MYOD介导的抑制与降低的H4 Kacme水平相关,而不是H3K27ac,表明一种新的表观遗传调节途径.
结论:
- MYOD具有作为转录激活器和抑制器的双重功能,挑战了既定的教条.
- 通过MYOD的E-box独立抑制提供了一个减少染色质可访问性的机制,并在肌体承诺期间保护细胞身份.
- 这些发现揭示了MYOD的功能多功能性及其在调节基因表达和细胞命运中的更广泛作用.
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
RNA Polymerase II Accessory Proteins
9.1K
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...
9.1K
Co-activators and Co-repressors
7.3K
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...
7.3K
Heterochromatin
10.8K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
10.8K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Chromatin Modification in iPS Cells
1.6K
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...
1.6K


