Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler

DOI PDF 被引用文献5件
  • Yu Chen
    Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 1
  • Yang Zhang
    Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 2
  • Yuchuan Wang
    Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 3
  • Liguo Zhang
    Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 1
  • Eva K. Brinkman
    Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, Netherlands 4
  • Stephen A. Adam
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 5
  • Robert Goldman
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 5
  • Bas van Steensel
    Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, Netherlands 4
  • Jian Ma
    Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 3
  • Andrew S. Belmont
    Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 1

説明

<jats:p>While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription “hot zones.” Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.</jats:p>

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