设计表观基因组编辑器:考虑生物化学和局部特异性
Z Begum Yagci1, Gautami R Kelkar1, Tyler J Johnson1
1Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA.
Methods in molecular biology (Clifton, N.J.)
|July 16, 2024
概括
表观基因组编辑器 (EEs) 为生物研究提供精确的染色质修饰. 本文详细介绍了在研究中优化EE生化和位置特异性的关键设计考虑因素.
科学领域:
- 染色体生物学 染色体生物学
- 分子表观遗传学 分子表观遗传学
- 基因组工程是基因组工程.
背景情况:
- 包括表观基因组编辑器 (EEs) 在内的局部特定蛋白质招募技术正在彻底改变染色体生物学.
- 在特定的内源性基因组位点上,EEs可以实现有针对性的生物化学修饰,从而促进功能研究.
研究的目的:
- 介绍和讨论表基因组编辑者的关键设计考虑和挑战.
- 引导研究人员优化EEs的生物化学和位点特异性,用于生物和转化应用.
主要方法:
- 对表观基因组编辑器的设计考虑的讨论.
- 分析影响位置特异性的因素,包括度,亲和力和热情.
- 探索能够考虑染色体复杂性的策略,避免隔离效应.
主要成果:
- 确定了在表观基因组编辑器中实现高位点特异性的关键因素.
- 概述了量化和提高EE特异性的方法.
- 强调需要管理EEs及其修改之间的相互依赖关系.
结论:
- 优化表观基因组编辑器设计对于准确的染色体修饰研究至关重要.
- 仔细考虑生化和位置特异性参数,提高了EEs在生物和转化研究中的实用性.
- 解决诸如分离和染色质多样性等挑战是推动该领域发展的关键.
相关概念视频
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Epigenetic Regulation
31.0K
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
31.0K
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
Histone Modification
13.2K
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...
13.2K
Restriction Enzymes
29.6K
Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
29.6K
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


