{"doi":"10.1016/j.tcb.2020.10.006","title":"Chromatin Tracing: Imaging 3D Genome and Nucleome","abstract":"Correct 3D genome organization is essential for the proper functioning of the genome. Recent advances in image-based 3D genomics techniques have enabled direct tracing of chromatin folding and multiplexed imaging of nucleome architectures in single cells of several important biological systems. Here, we discuss these advances and the future directions of image-based 3D genomics. Correct 3D genome organization is essential for the proper functioning of the genome. Recent advances in image-based 3D genomics techniques have enabled direct tracing of chromatin folding and multiplexed imaging of nucleome architectures in single cells of several important biological systems. Here, we discuss these advances and the future directions of image-based 3D genomics. The spatial organization of genomic DNA in the nucleus controls essential genome functions including gene expression regulation, DNA replication, mutation, repair, and recombination, and is crucially involved in many biomedical processes from development to diseases [1.Bonev B. Cavalli G. Organization and function of the 3D genome.Nat. Rev. Genet. 2016; 17: 661-678Crossref PubMed Scopus (404) Google Scholar, 2.Gibcus J.H. Dekker J. The hierarchy of the 3D genome.Mol. Cell. 2013; 49: 773-782Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar, 3.Schoenfelder S. Fraser P. Long-range enhancer–promoter contacts in gene expression control.Nat. Rev. Genet. 2019; 20: 437-455Crossref PubMed Scopus (219) Google Scholar]. To characterize the spatial genome organization, the sequencing-based high-throughput chromosome conformation capture (Hi-C) technique captures the contacts between genomic regions, and has led to a series of fundamental discoveries of genomic architectures, such as the A–B compartments and topologically associating domains (TADs) [1.Bonev B. Cavalli G. Organization and function of the 3D genome.Nat. Rev. Genet. 2016; 17: 661-678Crossref PubMed Scopus (404) Google Scholar, 2.Gibcus J.H. Dekker J. The hierarchy of the 3D genome.Mol. Cell. 2013; 49: 773-782Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar, 3.Schoenfelder S. Fraser P. Long-range enhancer–promoter contacts in gene expression control.Nat. Rev. Genet. 2019; 20: 437-455Crossref PubMed Scopus (219) Google Scholar], as well as allowing genome-wide profiling of promoter–enhancer interactions [3.Schoenfelder S. Fraser P. Long-range enhancer–promoter contacts in gene expression control.Nat. Rev. Genet. 2019; 20: 437-455Crossref PubMed Scopus (219) Google Scholar]. However, Hi-C cannot directly reveal the 3D positions of the genomic regions or the 3D chromatin folding path. Most Hi-C data provide the averaged contact frequency of many chromosome copies from different cells [1.Bonev B. Cavalli G. Organization and function of the 3D genome.Nat. Rev. Genet. 2016; 17: 661-678Crossref PubMed Scopus (404) Google Scholar,2.Gibcus J.H. Dekker J. The hierarchy of the 3D genome.Mol. Cell. 2013; 49: 773-782Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar]. Other sequencing methods revealed genomic architectures in association with nuclear components with important functional implications, including lamina-associated domains (LADs) and nucleolus-associated domains (NADs) [1.Bonev B. Cavalli G. Organization and function of the 3D genome.Nat. Rev. Genet. 2016; 17: 661-678Crossref PubMed Scopus (404) Google Scholar,2.Gibcus J.H. Dekker J. The hierarchy of the 3D genome.Mol. Cell. 2013; 49: 773-782Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar]. It has been challenging to combine the different sequencing-based methods to profile the multifaceted nucleome organization in the same cells. Alternatively, DNA fluorescence in situ hybridization (FISH) directly images the 3D positions of specific genomic loci and is intrinsically a single cell method [1.Bonev B. Cavalli G. Organization and function of the 3D genome.Nat. Rev. Genet. 2016; 17: 661-678Crossref PubMed Sc","journal":"Trends in Cell Biology","year":2020,"id":62974,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9387,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":270684,"name":"Siyuan Wang","orcid":"0000-0001-6550-4064","position":1,"is_corresponding":false},{"id":270682,"name":"Mengwei Hu","orcid":"0000-0003-0966-8720","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-18T21:11:00.632961Z","pmid":"33191055","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}