PDF(Pubmed)
Abstract：
The genome of a eukaryotic organism is comprised of a supra-molecular complex of chromatin fibers and intricately folded three-dimensional (3D) structures. Chromosomal interactions and topological changes in response to the developmental and/or environmental stimuli affect gene expression. Chromatin architecture plays important roles in DNA replication, gene expression, and genome integrity. Higher-order chromatin organizations like chromosome territories (CTs), A/B compartments, topologically associating domains (TADs), and chromatin loops vary among cells, tissues, and species depending on the developmental stage and/or environmental conditions (4D genomics). Every chromosome occupies a separate territory in the interphase nucleus and forms the top layer of hierarchical structure (CTs) in most of the eukaryotes. While the A and B compartments are associated with active (euchromatic) and inactive (heterochromatic) chromatin, respectively, having well-defined genomic/epigenomic features, TADs are the structural units of chromatin. Chromatin architecture like TADs as well as the local interactions between promoter and regulatory elements correlates with the chromatin activity, which alters during environmental stresses due to relocalization of the architectural proteins. Moreover, chromatin looping brings the gene and regulatory elements in close proximity for interactions. The intricate relationship between nucleotide sequence and chromatin architecture requires a more comprehensive understanding to unravel the genome organization and genetic plasticity. During the last decade, advances in chromatin conformation capture techniques for unravelling 3D genome organizations have improved our understanding of genome biology. However, the recent advances, such as Hi-C and ChIA-PET, have substantially increased the resolution, throughput as well our interest in analysing genome organizations. The present review provides an overview of the historical and contemporary perspectives of chromosome conformation capture technologies, their applications in functional genomics, and the constraints in predicting 3D genome organization. We also discuss the future perspectives of understanding high-order chromatin organizations in deciphering transcriptional regulation of gene expression under environmental stress (4D genomics). These might help design the climate-smart crop to meet the ever-growing demands of food, feed, and fodder.
摘要：
真核生物的基因组由染色质纤维的超分子复合物和复杂折叠的三维(3D)结构组成。响应发育和/或环境刺激的染色体相互作用和拓扑变化影响基因表达。染色质结构在DNA复制中起重要作用，基因表达，和基因组完整性。高阶染色质组织，如染色体区域(CT)，A/B舱,拓扑关联域(TAD)，染色质环因细胞而异，组织，和物种取决于发育阶段和/或环境条件（4D基因组学）。在大多数真核生物中，每个染色体在间期核中占据一个单独的区域，并形成分层结构（CT）的顶层。虽然A和B区室与活性（常色）和非活性（异色）染色质相关，分别,具有明确的基因组/表观基因组特征，TAD是染色质的结构单元。染色质结构如TAD以及启动子和调控元件之间的局部相互作用与染色质活性相关，由于结构蛋白的重新定位，在环境压力期间会发生变化。此外，染色质循环使基因和调控元件紧密接近以进行相互作用。核苷酸序列和染色质结构之间的复杂关系需要更全面的理解来解开基因组组织和遗传可塑性。在过去的十年里，用于解开3D基因组组织的染色质构象捕获技术的进展提高了我们对基因组生物学的理解.然而,最近的进步，如Hi-C和ChIA-PET，大大提高了分辨率，吞吐量以及我们对分析基因组组织的兴趣。本综述概述了染色体构象捕获技术的历史和当代观点，它们在功能基因组学中的应用，以及预测3D基因组组织的制约因素。我们还讨论了理解高阶染色质组织在环境胁迫下破译基因表达的转录调控的未来观点（4D基因组学）。这些可能有助于设计气候智能作物，以满足不断增长的食物需求，饲料，和饲料。
