Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories

Dietmar Rieder, Christian Ploner, Anne M. Krogsdam, Gernot Stocker, Maria Fischer, Marcel Scheideler, Christian Dani, Ez Zoubir Amri, Waltraud G. Müller, James G. McNally, Zlatko Trajanoski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Chromosomally separated, co-expressed genes can be in spatial proximity, but there is still debate about how this nuclear organization is achieved. Proposed mechanisms include global genome organization, preferential positioning of chromosome territories, or gene-gene sharing of various nuclear bodies. To investigate this question, we selected a set of genes that were co-expressed upon differentiation of human multipotent stem cells. We applied a novel multi-dimensional analysis procedure which revealed that prior to gene expression, the relative position of these genes was conserved in nuclei. Upon stem cell differentiation and concomitant gene expression, we found that co-expressed genes were closer together. In addition, we found that genes in the same 1-μm - diameter neighborhood associated with either the same splicing speckle or to a lesser extent with the same transcription factory. Dispersal of speckles by overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2 led to a significant drop in the number of genes in shared neighborhoods. We demonstrate quantitatively that the frequencies of speckle and factory sharing can be explained by assuming stochastic selection of a nuclear body within a restricted sub-volume defined by the original global gene positioning present prior to gene expression. We conclude that the spatial organization of these genes is a two-step process in which transcription-induced association with nuclear bodies enhances and refines a pre-existing global organization.

Original languageEnglish
Pages (from-to)1741-1759
Number of pages19
JournalCellular and Molecular Life Sciences
Issue number9
Publication statusPublished - May 2014


  • Nuclear organization
  • Spatial gene positioning
  • Splicing speckles
  • Transcription factories

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)
  • Experimental

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