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*

*Korrespondierende/r Autor/-in für diese Arbeit

Publikation: Beitrag in einer FachzeitschriftArtikelBegutachtung

Abstract

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.

Originalspracheenglisch
Seiten (von - bis)1741-1759
Seitenumfang19
FachzeitschriftCellular and Molecular Life Sciences
Jahrgang71
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - Mai 2014

ASJC Scopus subject areas

  • Molekularmedizin
  • Molekularbiologie
  • Pharmakologie
  • Zelluläre und Molekulare Neurowissenschaften
  • Zellbiologie

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)
  • Experimental

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