Abstract:
:The three-dimensional organization of the genome supports regulated gene expression, recombination, DNA repair, and chromosome segregation during mitosis. Chromosome conformation capture (Hi-C)1,2 analysis has revealed a complex genomic landscape of internal chromosomal structures in vertebrate cells3-7, but the identical sequence of sister chromatids has made it difficult to determine how they topologically interact in replicated chromosomes. Here we describe sister-chromatid-sensitive Hi-C (scsHi-C), which is based on labelling of nascent DNA with 4-thio-thymidine and nucleoside conversion chemistry. Genome-wide conformation maps of human chromosomes reveal that sister-chromatid pairs interact most frequently at the boundaries of topologically associating domains (TADs). Continuous loading of a dynamic cohesin pool separates sister-chromatid pairs inside TADs and is required to focus sister-chromatid contacts at TAD boundaries. We identified a subset of TADs that are overall highly paired and are characterized by facultative heterochromatin and insulated topological domains that form separately within individual sister chromatids. The rich pattern of sister-chromatid topologies and our scsHi-C technology will make it possible to investigate how physical interactions between identical DNA molecules contribute to DNA repair, gene expression, chromosome segregation, and potentially other biological processes.
journal_name
Naturejournal_title
Natureauthors
Mitter M,Gasser C,Takacs Z,Langer CCH,Tang W,Jessberger G,Beales CT,Neuner E,Ameres SL,Peters JM,Goloborodko A,Micura R,Gerlich DWdoi
10.1038/s41586-020-2744-4subject
Has Abstractpub_date
2020-10-01 00:00:00pages
139-144issue
7827eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2744-4journal_volume
586pub_type
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