THE SPATIAL-DISTRIBUTION OF HUMAN-IMMUNOGLOBULIN GENES WITHIN THE NUCLEUS - EVIDENCE FOR GENE TOPOGRAPHY INDEPENDENT OF CELL-TYPE AND TRANSCRIPTIONAL ACTIVITY

The three-dimensional positioning of immunoglobulin (Ig) genes within the nucleus of human cells was investigated using in situ hybridizatio n and confocal microscopy. The visualization of heavy and light chain genes in B-lymphoid cells showed that the three Ig genes are different ially and nonrandomly distributed in different nuclear subvolumes: the kappa-genes were found to be preferentially confined to an outer nucl ear volume, whereas the gamma and lambda genes consistently occupied m ore central positions within the nucleus, the lambda genes being more interior when compared with the gamma genes. The data further show tha t these overall topographical distributions are independent of gene tr anscriptional activity and are conserved in different cell types. Alth ough subtle gene movements within those defined topographical regions cannot be excluded by this study, the results indicate that tissue spe cificity of gene expression is not accompanied by drastic changes in g ene nuclear topography, rather suggesting that gene organization withi n the nucleus may be primarily dependent on structural constraints imp osed on the respective chromosomes.