Conformation of sister chromatids in the replicated human genome

Michael Mitter (), Catherina Gasser, Zsuzsanna Takacs, Christoph C. H. Langer, Wen Tang, Gregor Jessberger, Charlie T. Beales, Eva Neuner, Stefan L. Ameres, Jan-Michael Peters, Anton Goloborodko, Ronald Micura and Daniel W. Gerlich ()
Additional contact information
Michael Mitter: Vienna BioCenter
Catherina Gasser: Leopold-Franzens University
Zsuzsanna Takacs: Vienna BioCenter
Christoph C. H. Langer: Vienna BioCenter
Wen Tang: Vienna BioCenter
Gregor Jessberger: Vienna BioCenter
Charlie T. Beales: Vienna BioCenter
Eva Neuner: Leopold-Franzens University
Stefan L. Ameres: Vienna BioCenter
Jan-Michael Peters: Vienna BioCenter
Anton Goloborodko: Vienna BioCenter
Ronald Micura: Leopold-Franzens University
Daniel W. Gerlich: Vienna BioCenter

Nature, 2020, vol. 586, issue 7827, 139-144

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-2744-4

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