Projects per year
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.
Original language | English |
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Pages (from-to) | 139-144 |
Number of pages | 6 |
Journal | Nature |
Volume | 586 |
Issue number | 7827 |
DOIs | |
Publication status | Published - 1 Oct 2020 |
Austrian Fields of Science 2012
- 106023 Molecular biology
Keywords
- Cell Cycle Proteins/metabolism
- Chromatids/chemistry
- Chromosomal Proteins, Non-Histone/metabolism
- Chromosome Pairing
- DNA/analysis
- DNA Replication
- Genome, Human/genetics
- Heterochromatin/chemistry
- Humans
- Nucleic Acid Conformation
Projects
- 2 Active
-
RiboTrace: Bridging temporal resolution gaps to dissect RNA silencing at the molecular and genomic scale
1/01/22 → 31/01/25
Project: Research funding
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RNAdeco: decorating RNA for a purpose
Jantsch, M. F., Ameres, S. & Hofacker, I.
1/03/20 → 29/02/28
Project: Research funding