Ash1L对染色体环境的动态调节调节人类神经元结构和功能
bioRxiv : the preprint server for biology
|December 16, 2024
概括
组织素甲基转移酶ASH1L对大脑发育至关重要. 它的功能障碍导致神经元增长减少和基因失调,为神经精神疾病和潜在疗法提供了洞察力.
科学领域:
- 神经科学是一个神经科学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 精确的染色质调节通过组织素修饰是大脑发育和功能至关重要的.
- 基因组修饰酶的突变与复杂的大脑疾病有关.
- 涉及神经精神疾病的基因组甲基转移酶ASH1L,其病理生物学尚未得到充分研究.
研究的目的:
- 研究ASH1L在人类神经元发育中的作用及其与神经精神疾病的联系.
- 阐明ASH1L相关的病理生物学背后的分子机制.
- 确定与ASH1L相关疾病的潜在治疗策略.
主要方法:
- 产生具有ASH1L催化域突变的人类同源干细胞.
- 分析染色质配置文件,包括激活和抑制的基因素标记.
- 评估与神经元结构和功能相关的基因表达模式.
- 识别涉及转录因子和ASH1L的监管网络.
- 使用促进转录激活的表观遗传机制来拯救细胞缺陷.
主要成果:
- ASH1L功能障碍导致人体干细胞中神经元外生减少.
- 观察到与神经元功能相关的改变色素标记和失调的基因程序.
- 确定了一种涉及SP和克鲁佩尔样转录因子和ASH1L的新型调控轴.
- 通过表观遗传机制促进转录激活来挽救细胞缺陷.
结论:
- 通过表观遗传和转录轴,ASH1L在人类大脑发育中发挥着至关重要的作用.
- ASH1L功能障碍有助于复杂的大脑疾病的病理生物学.
- 这些发现为ASH1L相关的神经精神疾病的潜在治疗策略提供了洞察力.
相关概念视频
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
Chromatin Structure Regulates pre-mRNA Processing
6.9K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
6.9K
Spreading of Chromatin Modifications
8.2K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.2K
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Histone Modification
13.0K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.0K
Nucleosome Remodeling
9.0K
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...
9.0K


