Differences in the localization and morphology of chromosomes in the human nucleus.
Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.
Croft
J A
JA
MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Bridger
J M
JM
Boyle
S
S
Perry
P
P
Teague
P
P
Bickmore
W A
WA
D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002503:Centromere / Q000378:metabolism / Q000648:ultrastructure; D002887:Chromosomes, Human, Pair 18 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D002888:Chromosomes, Human, Pair 19 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D004247:DNA / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015530:Nuclear Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D003609:Dactinomycin; C012589:trichostatin A; D004004:Dichlororibofuranosylbenzimidazole; D004247:DNA; D012319:RNA Polymerase II; D006655:Histone Deacetylases