Open AccessConformation of sister chromatids in the replicated human genome
Author(s) -
Michael Mitter,
Catherina Gasser,
Zsuzsanna Takács,
Christoph C. H. Langer,
Wen Tang,
Gregor Jessberger,
Charlie T. Beales,
Eva Neuner,
Stefan L. Ameres,
JanMichael Peters,
Anton Goloborodko,
Ronald Micura,
Daniel W. Gerlich
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2744-4
Subject(s) - sister chromatids , cohesin , chromatid , genetics , chromosome segregation , biology , genome , sister chromatid exchange , dna , chromosome , gene
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 cells 3-7 , 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.