title: Nucleolar association and transcriptional inhibition through 5S rDNA in mammals.
abstract: Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals.
authors.affiliation: Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fedoriw
authors.forename: Joshua
authors.initials: J
authors.lastname: Starmer
authors.forename: Della
authors.initials: D
authors.lastname: Yee
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002466:Cell Nucleolus / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics*; D004275:DNA, Ribosomal / Q000235:genetics*; D003609:Dactinomycin / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D006570:Heterochromatin / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011544:Pseudogenes / Q000235:genetics; D012318:RNA Polymerase I / Q000187:drug effects; D012341:RNA, Ribosomal, 5S / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics
chemical_list: D002843:Chromatin; D004275:DNA, Ribosomal; D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D012341:RNA, Ribosomal, 5S; D014157:Transcription Factors; D003609:Dactinomycin; D011495:Histone-Lysine N-Methyltransferase; D012318:RNA Polymerase I