Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation.

Autor: Fraser J; Department of Biochemistry, Goodman Cancer Centre, McGill University, Montréal, QC, Canada., Ferrai C; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany Genome Function Group, MRC Clinical Sciences Centre, Imperial College London Hammersmith Hospital Campus, London, UK., Chiariello AM; Dipartimento di Fisica, Università di Napoli Federico II INFN Napoli CNR-SPIN Complesso Universitario di Monte Sant'Angelo, Naples, Italy., Schueler M; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany., Rito T; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany., Laudanno G; Dipartimento di Fisica, Università di Napoli Federico II INFN Napoli CNR-SPIN Complesso Universitario di Monte Sant'Angelo, Naples, Italy., Barbieri M; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany., Moore BL; MRC Human Genetics Unit, MRC IGMM University of Edinburgh, Edinburgh, UK., Kraemer DC; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany., Aitken S; MRC Human Genetics Unit, MRC IGMM University of Edinburgh, Edinburgh, UK., Xie SQ; Genome Function Group, MRC Clinical Sciences Centre, Imperial College London Hammersmith Hospital Campus, London, UK., Morris KJ; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany Genome Function Group, MRC Clinical Sciences Centre, Imperial College London Hammersmith Hospital Campus, London, UK., Itoh M; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako Saitama, Japan Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama Kanagawa, Japan., Kawaji H; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako Saitama, Japan Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama Kanagawa, Japan., Jaeger I; Stem Cell Neurogenesis Group, MRC Clinical Sciences Centre, Imperial College London Hammersmith Hospital Campus, London, UK., Hayashizaki Y; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako Saitama, Japan., Carninci P; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama Kanagawa, Japan., Forrest AR; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama Kanagawa, Japan., Semple CA; MRC Human Genetics Unit, MRC IGMM University of Edinburgh, Edinburgh, UK colin.semple@igmm.ed.ac.uk josee.dostie@mcgill.ca ana.pombo@mdc-berlin.de mario.nicodemi@na.infn.it., Dostie J; Department of Biochemistry, Goodman Cancer Centre, McGill University, Montréal, QC, Canada colin.semple@igmm.ed.ac.uk josee.dostie@mcgill.ca ana.pombo@mdc-berlin.de mario.nicodemi@na.infn.it., Pombo A; Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany Genome Function Group, MRC Clinical Sciences Centre, Imperial College London Hammersmith Hospital Campus, London, UK colin.semple@igmm.ed.ac.uk josee.dostie@mcgill.ca ana.pombo@mdc-berlin.de mario.nicodemi@na.infn.it., Nicodemi M; Dipartimento di Fisica, Università di Napoli Federico II INFN Napoli CNR-SPIN Complesso Universitario di Monte Sant'Angelo, Naples, Italy colin.semple@igmm.ed.ac.uk josee.dostie@mcgill.ca ana.pombo@mdc-berlin.de mario.nicodemi@na.infn.it.
Jazyk: angličtina
Zdroj: Molecular systems biology [Mol Syst Biol] 2015 Dec 23; Vol. 11 (12), pp. 852. Date of Electronic Publication: 2015 Dec 23.
DOI: 10.15252/msb.20156492
Abstrakt: Mammalian chromosomes fold into arrays of megabase-sized topologically associating domains (TADs), which are arranged into compartments spanning multiple megabases of genomic DNA. TADs have internal substructures that are often cell type specific, but their higher-order organization remains elusive. Here, we investigate TAD higher-order interactions with Hi-C through neuronal differentiation and show that they form a hierarchy of domains-within-domains (metaTADs) extending across genomic scales up to the range of entire chromosomes. We find that TAD interactions are well captured by tree-like, hierarchical structures irrespective of cell type. metaTAD tree structures correlate with genetic, epigenomic and expression features, and structural tree rearrangements during differentiation are linked to transcriptional state changes. Using polymer modelling, we demonstrate that hierarchical folding promotes efficient chromatin packaging without the loss of contact specificity, highlighting a role far beyond the simple need for packing efficiency.
(© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
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