Genome-wide mapping and analysis of chromosome architecture

Anthony D. Schmitt, Ming Hu, Bing Ren
2016 Nature reviews. Molecular cell biology  
Chromosomes of eukaryotes adopt highly dynamic and complex hierarchical structures in the nucleus. The three-dimensional (3D) organization of chromosomes profoundly affects DNA replication, transcription and the repair of DNA damage. Thus, a thorough understanding of nuclear architecture is fundamental to the study of nuclear processes in eukaryotic cells. Recent years have seen rapid proliferation of technologies to investigate genome organization and function. Here, we review experimental and
more » ... computational methodologies for 3D genome analysis, with special focus on recent advances in high-throughput chromatin conformation capture (3C) techniques and data analysis. Recent studies have revealed the existence of millions of potential cis-regulatory elements in the human genome, with a great number of them residing in intergenic regions and away from their target gene promoters 1,2 . The distal elements, which largely consist of enhancers, influence the transcription of target genes through looping of chromatin fibres 3-11 during animal development 12-16 . Evidence of chromatin looping has been detected for many enhancers 17-21 . However, the mechanisms by which chromatin interactions are formed and maintained during development remain to be elucidated. The chromosome conformation capture (3C) method and its studying chromatin interactions in eukaryotic cells [22] [23] [24] [25] [26] [27] (TABLE 1) . These techniques have uncovered general features of genome organization, which include the existence of hierarchical chromatin structures, such as compartments 22 , topologically associating domains (TADs) 6,10 , sub-TADs 11 , insulated domains 17 and chromatin loops 27 .However, different C-technologies and analysis strategies
doi:10.1038/nrm.2016.104 pmid:27580841 pmcid:PMC5763923 fatcat:2eyv2yjh2rcc5nbzpmvtv5bv2a