Differences in the localization and morphology of chromosomes in the humannucleus

Using fluorescence in situ hybridization we show striking differences in nu clear position, chromosome morphology, and interactions with nuclear substr ucture for human chromosomes 18 and 19, Human chromosome 19 is shown to ado pt a more internal position in the nucleus than chromosome 18 and to be mor e extensively associated with the nuclear matrix, The more peripheral local ization of chromosome 18 is established early in the cell cycle and is main tained thereafter. We show that the preferential localization of chromosome s 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcr iption can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chr omosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartme ntalized.