title: The spatial dynamics of tissue-specific promoters during C. elegans development.
abstract: To understand whether the spatial organization of the genome reflects the cell's differentiated state, we examined whether genes assume specific subnuclear positions during Caenorhabditis elegans development. Monitoring the radial position of developmentally controlled promoters in embryos and larval tissues, we found that small integrated arrays bearing three different tissue-specific promoters have no preferential position in nuclei of undifferentiated embryos. However, in differentiated cells, they shifted stably toward the nuclear lumen when activated, or to the nuclear envelope when silent. In contrast, large integrated arrays bearing the same promoters became heterochromatic and nuclear envelope-bound in embryos. Tissue-specific activation of promoters in these large arrays in larvae overrode the perinuclear anchorage. For transgenes that carry both active and inactive promoters, the inward shift of the active promoter was dominant. Finally, induction of master regulator HLH-1 prematurely induced internalization of a muscle-specific promoter array in embryos. Fluorescence in situ hybridization confirmed analogous results for the endogenous endoderm-determining gene pha-4. We propose that, in differentiated cells, subnuclear organization arises from the selective positioning of active and inactive developmentally regulated promoters. We characterize two forces that lead to tissue-specific subnuclear organization of the worm genome: large repeat-induced heterochromatin, which associates with the nuclear envelope like repressed genes in differentiated cells, and tissue-specific promoters that shift inward in a dominant fashion over silent promoters, when they are activated.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Meister
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Towbin
authors.forename: Brietta L
authors.initials: BL
authors.lastname: Pike
authors.forename: Aaron
authors.initials: A
authors.lastname: Ponti
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003094:Collagen / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics; D008957:Models, Genetic; D032342:Muscle Cells / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D006570:Heterochromatin; C113277:Pha-4 protein, C elegans; D015534:Trans-Activators; C098282:rol-6 protein, C elegans; D003094:Collagen
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