空间3D基因组组织控制在人类神经发生过程中双价染色素的活性
Sajad Hamid Ahanger1,2, Chujing Zhang1,2, Evan R Semenza1,2
1Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
bioRxiv : the preprint server for biology
|August 12, 2024
概括
人类大脑中的空间基因组组织在发育过程中被重塑. 从核膜转移基因到斑点显著增加神经元基因表达,揭示了表观遗传学调节的新范式.
科学领域:
- 基因组学就是基因组学.
- 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.
背景情况:
- 核基因组呈现出三维 (3D) 结构,染色体域与核膜和核斑点等亚核区相互作用.
- 由于技术挑战,空间基因组架构在人类大脑发育中的作用在很大程度上未被探索.
研究的目的:
- 为了研究空间基因组组织如何调节人类大脑发育.
- 为了绘制基因组相互作用与人类皮层神经细胞的核膜和斑点.
主要方法:
- 基因组相互作用的高分辨率地图的生成.
- 细胞从神经性血统中隔离在人类中期皮质中的细胞.
- 与亚核局部化相关的染色质状态和基因转录的分析.
主要成果:
- 空间基因组组织的广泛重塑发生在皮层神经发生过程中.
- 数百个神经元基因,包括关键的神经发育基因,从核膜转移到核斑点.
- 转移到斑点增强双价色染色质分辨率到H3K4me3,增加了7倍以上的转录.
- 靠近核外围,而不是H3K27me3,是维持膜相关双价基因平衡状态的主要因素.
结论:
- 亚核基因组细分在人类大脑发育期间的神经性转录调节中起着关键作用.
- 基因在核中的位置对于理解其表观基因组调节至关重要,建立了一个新的范式.
相关概念视频
Chromatin Position Affects Gene Expression
23.3K
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...
23.3K
Inheritance of Chromatin Structures
6.2K
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...
6.2K
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 Packaging
16.6K
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
16.6K


