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Ultrastructural Details of Mammalian Chromosome Architecture

Krietenstein, Nils ; Abraham, Sameer ; Venev, Sergey V. ; Abdennur, Nezar ; Gibcus, Johan ; Hsieh, Tsung-Han S. ; Parsi, Krishna Mohan ; Yang, Liyan ; Maehr, René ; Mirny, Leonid A. ; Dekker, Job ; Rando, Oliver J.

Molecular cell, 2020-05, Vol.78 (3), p.554-565.e7 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    Ultrastructural Details of Mammalian Chromosome Architecture
  • Autor: Krietenstein, Nils ; Abraham, Sameer ; Venev, Sergey V. ; Abdennur, Nezar ; Gibcus, Johan ; Hsieh, Tsung-Han S. ; Parsi, Krishna Mohan ; Yang, Liyan ; Maehr, René ; Mirny, Leonid A. ; Dekker, Job ; Rando, Oliver J.
  • Assuntos: Animals ; CCCTC-Binding Factor - metabolism ; Cells, Cultured ; Chromatin ; Chromatin - chemistry ; Chromosomes ; Chromosomes, Human - ultrastructure ; Chromosomes, Mammalian - ultrastructure ; CTCF ; Embryonic Stem Cells - cytology ; Fibroblasts - cytology ; Humans ; Loop extrusion ; Male ; Mammals - genetics ; Micro-C ; Nucleosomes - metabolism ; Nucleosomes - ultrastructure ; Signal-To-Noise Ratio
  • É parte de: Molecular cell, 2020-05, Vol.78 (3), p.554-565.e7
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Lead Contact
    Cells were cultured and fixed by MP, RM, and LY. Hi-C was performed by JG and LY. Micro-C was performed by NK after training by T-HS. Data analysis was performed by NK, SV, SA, and NA, with supervision by LM, JD, and OJR. NK carried out the majority of analyses in Figures 1–3, with the exception of compartment calls and interaction decay curves by NA and SA. Loop anchor calls were carried out by SV, with SA and NA generating detailed analyses of new loop anchors. Manuscript was written by NK and OJR, and edited by all authors.
    AUTHOR CONTRIBUTIONS
  • Descrição: Over the past decade, 3C-related methods have provided remarkable insights into chromosome folding in vivo. To overcome the limited resolution of prior studies, we extend a recently developed Hi-C variant, Micro-C, to map chromosome architecture at nucleosome resolution in human ESCs and fibroblasts. Micro-C robustly captures known features of chromosome folding including compartment organization, topologically associating domains, and interactions between CTCF binding sites. In addition, Micro-C provides a detailed map of nucleosome positions and localizes contact domain boundaries with nucleosomal precision. Compared to Hi-C, Micro-C exhibits an order of magnitude greater dynamic range, allowing the identification of ∼20,000 additional loops in each cell type. Many newly identified peaks are localized along extrusion stripes and form transitive grids, consistent with their anchors being pause sites impeding cohesin-dependent loop extrusion. Our analyses comprise the highest-resolution maps of chromosome folding in human cells to date, providing a valuable resource for studies of chromosome organization. [Display omitted] •Micro-C provides nucleosome resolution maps of chromosome folding•The resolution and signal-to-noise are significantly improved relative to Hi-C•Thousands of new loops are identified, suggesting weak pauses to loop extrusion•New loops suggest TADs represent heterogeneous collections of transient loops Krietenstein et al. extend analyses of chromosome folding to nucleosome resolution in human cells. These ultra-deep Micro-C maps capture known features of chromosomes with improved signal-to-noise, identifying tens of thousands of new looping interactions. Newly identified loops reveal weak pause sites along cohesin extrusion tracks, providing insight into TAD structural heterogeneity.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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