Large-scale chromatin organization of the major histocompatibility complexand other regions of human chromosome 6 and its response to interferon in interphase nuclei

The large-scale chromatin organization of the major histocompatibility comp lex and other regions of chromosome 6 was studied by three-dimensional imag e analysis in human cell types with major differences in transcriptional ac tivity. Entire gene clusters were visualized by fluorescence in situ hybrid ization with multiple locus-specific probes. Individual genomic regions sho wed distinct configurations in relation to the chromosome 6 terrritory. Lar ge chromatin loops containing several megabases of DNA were observed extend ing outwards from the surface of the domain defined by the specific chromos ome 6 paint. The frequency with which a genomic region was observed on an e xternal chromatin loop was cell type dependent and appeared to be related t o the number of active genes in that region. Transcriptional up-regulation of genes in the major histocompatibility complex by interferon-gamma led to an increase in the frequency with which this large gene cluster was found on an external chromatin loop. Our data are consistent with an association between large-scale chromatin organization of specific genomic regions and their transcriptional status.