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

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 bodi...

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Veröffentlicht in:	Cellular and molecular life sciences : CMLS Jg. 71; H. 9; S. 1741 - 1759
Hauptverfasser:	Rieder, Dietmar, Ploner, Christian, Krogsdam, Anne M, Stocker, Gernot, Fischer, Maria, Scheideler, Marcel, Dani, Christian, Amri, Ez-Zoubir, Müller, Waltraud G, McNally, James G, Trajanoski, Zlatko
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Basel Springer-Verlag 01.05.2014 Springer Basel Springer Nature B.V Springer Verlag
Schlagworte:	Biochemistry Biomedical and Life Sciences Biomedicine Cdc2 protein Cell Biology Cell differentiation Cell Nucleus - metabolism Cells, Cultured chromosomes Chromosomes - metabolism Development Biology Differentiation (biology) Dimensional analysis DNA-directed RNA polymerase Extracellular Matrix Proteins - genetics Extracellular Matrix Proteins - metabolism Gene expression gene overexpression Genes HEK293 Cells Humans Kinases Life Sciences Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Nuclear Proteins - genetics Nuclear Proteins - metabolism Polymerase chain reaction Protein kinase C Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Recombinant Fusion Proteins - biosynthesis Recombinant Fusion Proteins - genetics Research Article Ribonucleic acid Ribonucleoproteins - genetics Ribonucleoproteins - metabolism RNA RNA polymerase II RNA Polymerase II - genetics RNA Polymerase II - metabolism Serine-Arginine Splicing Factors Stem cells Stochastic models Tacrolimus Binding Proteins - genetics Tacrolimus Binding Proteins - metabolism transcription (genetics) Spatial gene positioning Splicing speckles Transcription factories Nuclear organization
ISSN:	1420-682X, 1420-9071, 1420-9071
Online-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	http://dx.doi.org/10.1007/s00018-013-1465-3 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC8372199
ISSN:	1420-682X 1420-9071 1420-9071
DOI:	10.1007/s00018-013-1465-3