染色体空间构象研究:技术、应用与挑战

Chromosome Spatial Conformation:Techniques,Applications and Challenges

染色体在细胞核中的空间构象对于基因的表达、DNA的复制、DNA的损伤修复以及基因的稳定性具有至关重要的作用,了解染色体在细胞核中的空间构象是研究疾病发生发展的关键所在。但目前对于染色体空间构象的变化规律的认识依然不足,束缚了对染色体空间构象与疾病关系的研究。其主要原因在于高分辨率研究染色体空间构象的技术有待进一步发展与完善。本文简要介绍了染色体的基本空间组织结构,并详细介绍了非活体细胞染色体空间构象研究技术荧光原位杂交技术(FISH)和染色体构象捕获技术(3C及其衍生技术)的应用及相关研究成果。为了能够更加准确地实时观察染色体的空间构象及其动态变化,采用活体细胞进行研究势在必行,因此,本文又详细介绍了基于荧光显微技术的定位追踪技术,以及染色体动力学追踪技术在染色体空间构象研究方面的应用及相关成果。最后,针对各种技术的优缺点,本文对目前各种技术研究染色体空间构象存在的问题以及对今后的研究方向给出了建议。

The spatial conformation of chromosomes within the nucleus plays a pivotal role in gene expression,DNA replication,DNA damage repair,and gene stability.Understanding the intricate spatial organization of chromosomes is crucial for studying disease occurrence and development.However,our current understanding of changes in chromosome spatial conformation remains insufficient,limiting our ability to investigate the relationship between chromosomal structure and disease.This limitation primarily stems from the need for further development and refinement of high-resolution techniques used to study chromosome spatial conformation.In this paper,we provide a brief overview of the fundamental spatial structure of chromosomes before delving into detailed discussions on the application of fluorescence in situ hybridization(FISH),chromosome conformation capture(3C)and its derivatives,along with relevant research findings.To achieve more accurate real-time observations of chromosomal dynamics and spatial organization,it is imperative to conduct experiments using live cells.Therefore,this paper provides an extensive description of how fluorescence microscopy-based location tracking technology and chromosome dynamic tracking technology have been applied in studying chromosomal spatial conformation as well as highlighting notable achievements in this field.Finally,based on evaluating the strengths and weaknesses associated with various techniques employed thus far,we identify existing challenges within chromosomal spatial conformation studies while offering suggestions for future research endeavors.