REST高度依赖的染色体重塑和替代的Grk6转录合成过度激活了小脑颗粒细胞原始体中的Cxcr4-Sdf1信号
Keri Callegari1, Jyothishmathi Swaminathan1, Lei Guo2
1Department of Pediatrics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
RE1沉默转录因子 (REST) 通过控制转录多样性来调节神经发生. 在小脑细胞中增加的REST会改变G蛋白结合受体激酶-6 (Grk6) 拼接,通过Cxcr4信号增强细胞迁移.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- RE1沉默转录因子 (REST) 是一个已知的抑制基因,对神经发生至关重要.
- 大脑小粒细胞原始体 (CGNPs) 迁移对小脑发育至关重要,并依赖于诸如C-X-C基因受体4 (Cxcr4) 信号传递等途径.
研究的目的:
- 调查REST在调控CGNP迁移和转录多样性的作用.
- 阐明REST影响Cxcr4信号和CGNP行为的分子机制.
主要方法:
- 在RESTTG小鼠中,有条件的REST升高.
- 对CGNP迁移,叶子和Cxcr4信号的分析.
- RNA测序和多原子分析以确定转录组变化和调节元素.
- 对G蛋白结合受体激酶-6 (Grk6) 异型的结构建模.
- 药理上抑制了增强剂的味 (Ezh2).
主要成果:
- 在CGNP中条件REST的升高扰乱了小脑叶和增加了细胞迁移.
- REST控制的转录多样性,包括Cxcr4调节器Grk6的替代拼接,导致对缺少外形10a的异形 (Grk6-207) 的上调调节.
- Grk6-207表达过度激活了Cxcr4信号和增强了CGNP化学反应,表明信号脱敏受损.
- REST的升高增加了Grk6外因子10a-10b结处的染色质可访问性,促进了外因子10a的排除.
- 鉴定出增强性肠道同类物2 (Ezh2) 是一个关键的调解物,在Grk6位点表现出增加的占用率,并调节Grk6-207表达和CGNP迁移.
结论:
- 在神经发生过程中,REST在调节转录多样性和外因子跳转方面发挥着新的作用.
- Grk6的REST介导的替代拼接显著影响了Cxcr4信号和CGNP迁移.
- Ezh2在REST的下游作用,控制Grk6的替代拼接和随后的CGNP迁移,突出了小脑发育的新监管轴.
关键词:
ATACseqqseq ATACseqseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq ATACseq在Cxcr4-SDF1信号传输中.这就是 Ezh2 2 的意思.格里克6 格里克6 的意思休息时间 休息时间在RNA-seqqq.其他替代的成绩单.细胞迁移 细胞迁移更多相关视频
09:07Genetic Manipulation of Cerebellar Granule Neurons In Vitro and In Vivo to Study Neuronal Morphology and Migration
Published on: March 17, 2014
14.2K
04:20Utilizing In Vivo Postnatal Electroporation to Study Cerebellar Granule Neuron Morphology and Synapse Development
Published on: June 9, 2021
3.0K
相关概念视频
01:32Chromatin Modification in iPS Cells
2.1K
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...
2.1K
01:29Somatic to iPS Cell Reprogramming
2.6K
Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
2.6K
02:54Nucleosome Remodeling
10.7K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.7K
02:23Master Transcription Regulators
7.7K
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...
7.7K
03:17Inheritance of Chromatin Structures
7.2K
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...
7.2K
02:35Chromatin Position Affects Gene Expression
24.6K
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
24.6K