| Autor: |
Mitter M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria. michael.mitter@imba.oeaw.ac.at., Gasser C; Institute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Leopold-Franzens University, Innsbruck, Austria., Takacs Z; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria., Langer CCH; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria., Tang W; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Jessberger G; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Beales CT; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria., Neuner E; Institute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Leopold-Franzens University, Innsbruck, Austria., Ameres SL; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria., Peters JM; Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria., Goloborodko A; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria.; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA., Micura R; Institute of Organic Chemistry and Center for Molecular Biosciences (CMBI), Leopold-Franzens University, Innsbruck, Austria., Gerlich DW; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Vienna, Austria. daniel.gerlich@imba.oeaw.ac.at. |
| Abstrakt: |
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. |
Full text from SpringerLink