title: Co-expressed genes prepositioned in spatial neighborhoods stochastically associate with SC35 speckles and RNA polymerase II factories.
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.
authors.affiliation: Division of Bioinformatics, Biocenter, Innsbruck Medical University, Innrain 80, 6020, Innsbruck, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rieder
authors.forename: Christian
authors.initials: C
authors.lastname: Ploner
authors.forename: Anne M
authors.initials: AM
authors.lastname: Krogsdam
authors.forename: Gernot
authors.initials: G
authors.lastname: Stocker
authors.forename: Maria
authors.initials: M
authors.lastname: Fischer
authors.forename: Marcel
authors.initials: M
authors.lastname: Scheideler
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.forename: Ez-Zoubir
authors.initials: EZ
authors.lastname: Amri
authors.forename: Waltraud G
authors.initials: WG
authors.lastname: Müller
authors.forename: James G
authors.initials: JG
authors.lastname: McNally
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Trajanoski
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002875:Chromosomes / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D012319:RNA Polymerase II; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C122166:SPON2 protein, human; C073288:SRSF2 protein, human; C066780:Clk dual-specificity kinases
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