Conformation of sister chromatids in the replicated human genome (2024)

Mitter, M., Gasser, C., Takacs, Z., Langer, C. C. H., Tang, W., Jessberger, G., Beales, C. T., Neuner, E., Ameres, S. L., Peters, J-M., Goloborodko, A., Micura, R. (2020). Conformation of sister chromatids in the replicated human genome. Nature, 586(7827), 139-144. https://doi.org/10.1038/s41586-020-2744-4

Mitter, Michael ; Gasser, Catherina ; Takacs, Zsuzsanna et al. / Conformation of sister chromatids in the replicated human genome. In: Nature. 2020 ; Vol. 586, No. 7827. pp. 139-144.

@article{8f4a042d8cc14a0881f2a9a89043f86b,

title = "Conformation of sister chromatids in the replicated human genome",

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.",

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",

author = "Michael Mitter and Catherina Gasser and Zsuzsanna Takacs and Langer, {Christoph C H} and Wen Tang and Gregor Jessberger and Beales, {Charlie T} and Eva Neuner and Ameres, {Stefan L} and Jan-Michael Peters and Anton Goloborodko and Ronald Micura and Gerlich, {Daniel W}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = oct,

day = "1",

doi = "10.1038/s41586-020-2744-4",

language = "English",

volume = "586",

pages = "139--144",

journal = "Nature",

issn = "0028-0836",

publisher = "NATURE PUBLISHING GROUP",

number = "7827",

}

Mitter, M, Gasser, C, Takacs, Z, Langer, CCH, Tang, W, Jessberger, G, Beales, CT, Neuner, E, Ameres, SL, Peters, J-M, Goloborodko, A, Micura, R 2020, 'Conformation of sister chromatids in the replicated human genome', Nature, vol. 586, no. 7827, pp. 139-144. https://doi.org/10.1038/s41586-020-2744-4

Conformation of sister chromatids in the replicated human genome. / Mitter, Michael; Gasser, Catherina; Takacs, Zsuzsanna et al.

In: Nature, Vol. 586, No. 7827, 01.10.2020, p. 139-144.

Publications: Contribution to journal › Article › Peer Reviewed

TY - JOUR

T1 - Conformation of sister chromatids in the replicated human genome

AU - Mitter, Michael

AU - Gasser, Catherina

AU - Takacs, Zsuzsanna

AU - Langer, Christoph C H

AU - Tang, Wen

AU - Jessberger, Gregor

AU - Beales, Charlie T

AU - Neuner, Eva

AU - Ameres, Stefan L

AU - Peters, Jan-Michael

AU - Goloborodko, Anton

AU - Micura, Ronald

AU - Gerlich, Daniel W

N1 - Publisher Copyright:© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/10/1

Y1 - 2020/10/1

N2 - 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.

AB - 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.

KW - Cell Cycle Proteins/metabolism

KW - Chromatids/chemistry

KW - Chromosomal Proteins, Non-Histone/metabolism

KW - Chromosome Pairing

KW - DNA/analysis

KW - DNA Replication

KW - Genome, Human/genetics

KW - Heterochromatin/chemistry

KW - Humans

KW - Nucleic Acid Conformation

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U2 - 10.1038/s41586-020-2744-4

DO - 10.1038/s41586-020-2744-4

M3 - Article

C2 - 32968280

VL - 586

SP - 139

EP - 144

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7827

ER -

Mitter M, Gasser C, Takacs Z, Langer CCH, Tang W, Jessberger G et al. Conformation of sister chromatids in the replicated human genome. Nature. 2020 Oct 1;586(7827):139-144. doi: 10.1038/s41586-020-2744-4