Conformation of sister chromatids in the replicated human genome.
Nature
; 586(7827): 139-144, 2020 10.
Article
in En
| MEDLINE
| ID: mdl-32968280
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome, Human
/
Chromatids
/
Chromosome Pairing
/
DNA Replication
/
Nucleic Acid Conformation
Limits:
Humans
Language:
En
Journal:
Nature
Year:
2020
Type:
Article
Affiliation country:
Austria