title: Stably integrated and expressed retroviral sequences can influence nuclear location and chromatin condensation of the integration locus.
abstract: The large-scale chromatin organization of retrovirus and retroviral gene vector integration loci has attracted little attention so far. We compared the nuclear organization of transcribed integration loci with the corresponding loci on the homologous chromosomes. Loci containing gamma-retroviral gene transfer vectors in mouse hematopoietic precursor cells showed small but significant repositioning of the integration loci towards the nuclear interior. HIV integration loci in human cells showed a significant repositioning towards the nuclear interior in two out of five cases. Notably, repositioned HIV integration loci also showed chromatin decondensation. Transcriptional activation of HIV by sodium butyrate treatment did not lead to a further enhancement of the differences between integration and homologous loci. The positioning relative to splicing speckles was indistinguishable for integration and homologous control loci. Our data show that stable retroviral integration can lead to alterations of the nuclear chromatin organization, and has the potential to modulate chromatin structure of the host cell. We thus present an example where a few kb of exogenous DNA are sufficient to significantly alter the large-scale chromatin organization of an endogenous locus.
authors.affiliation: Department Biologie II, Ludwig-Maximilians-Universität München, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Nagel
authors.forename: Birgit
authors.initials: B
authors.lastname: Gross
authors.forename: Manja
authors.initials: M
authors.lastname: Meggendorfer
authors.forename: Carolin
authors.initials: C
authors.lastname: Preiss
authors.forename: Manuel
authors.initials: M
authors.lastname: Grez
authors.forename: Ruth
authors.initials: R
authors.lastname: Brack-Werner
authors.forename: Steffen
authors.initials: S
authors.lastname: Dietzel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D056426:Genetic Loci; D005822:Genetic Vectors; D005910:Glioma / Q000473:pathology; D006678:HIV / Q000235:genetics*; D006367:HeLa Cells; D006410:Hematopoiesis; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019154:Protein Splicing; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016662:Virus Integration / Q000235:genetics*
chemical_list: D006570:Heterochromatin; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors