Abstract
Recent sequence-based profiling technologies such as high-throughput sequencing to detect fragment nucleotide sequence (Hi-C) and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) have revolutionized the field of three-dimensional (3D) chromatin architecture. It is now recognized that human genome functions as folded 3D chromatin units and looping paradigm is the basic principle of gene regulation. To better interpret the 3D data dramatically accumulating in past five years and to gain deep biological insights, huge efforts have been made in developing novel quantitative analysis methods. However, the full understanding of genome regulation requires thorough knowledge in both genomic technologies and their related data analyses. We summarize the recent advances in genomic technologies in identifying the 3D chromatin structure and interaction, and illustrate the quantitative analysis methods to infer functional domains and chromatin interactions, and further elucidate the emerging single-cell Hi-C technique and its computational analysis, and finally discuss the future directions such as advances of 3D chromatin techniques in diseases.
Highlights
The diverse cell types of an organism share the same DNA information, their genomes undergo quite different structural and organizational changes during differentiation and replication; and such changes affect gene expression and cellular functions via different information routes.In vivo, human genome functions as a folded three-dimensional (3D) chromatin polymer.Nearly half a century ago, gene position on a single chromosome was considered a main determinant of gene activity due to the lack of an advanced profiling technique
3C-based technique and its extensions, such as Capture on Chip (4C) [29,30], techniques generally cover multiplexed 3C sequencing (3C-seq) [32], 4C combined with highthroughput sequencing (4C-seq) [33], capture-C [34], high-throughput sequencing to detect fragment nucleotide sequence (Hi-C) [3], Tethered Conformation Capture (TCC)
The sequencing-based techniques generally cover multiplexed 3C sequencing (3C-seq) [32], 4C combined with high-throughput sequencing (4C-seq) [33], capture-C [34], Hi-C [3], Tethered Conformation Capture (TCC) [35], and Targeted Chromatin Capture (T2C) [36]
Summary
The diverse cell types of an organism share the same DNA information, their genomes undergo quite different structural and organizational changes during differentiation and replication; and such changes affect gene expression and cellular functions via different information routes. More functionally diversified regulatory elements (REs), including enhancers, silencers, insulators, and boundaries, have been identified to act collaboratively with active promoters via long range tethering or chromatin looping mechanisms [4]. Homeotic complex D (HoxD), with up to 13 homeobox gene paralogs following collinearity in organization and expression, is regulated with the sequential chromatin opening and promoter-enhancer looping. We summarize the recent advances in genomic technologies in identifying 3D chromatin structure and interaction, and illustrate the quantitative analysis methods on processing data and inferring functional domains or chromatin interactions, and further elucidate the newly emerging single-cell Hi-C technique and its computational analysis, and discuss the future directions such as advances of 3D chromatin profiling technique in diseases
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