Spatial organization of housekeeping genes in interphase nuclei

The spatial organization of the eukaryotic genome is closely related to its function. In particular, interactions of gene promoters with distant enhancer elements in active chromatin hubs and gene recruitment to common transcription factories play an important role in regulating gene transcription. Tissue-specific genes are mostly used as models to study the spatial interactions of genomic regulatory elements, while little is known as to what extent the spatial organization of chromosomes is guided by housekeeping genes, which are transcribed in the majority of cells and are considerably more abundant than transcribed tissue-specific genes. To address the issue, chromosome conformation capture on chip (4C) was employed in a genomewide probing of spatial contacts for the chicken housekeeping genes CARHSP1 and TRAP1, which are on chromosome 14. Their promoters showed a higher frequency of interactions with transcriptionally active chromosome regions and regions enriched in Sp1 general transcription factor-binding sites and CpG islands, which both mark the promoters of housekeeping genes. No such preferences were observed for a gene-poor chromosome 14 region. Further evidence for the association of housekeeping gene promoters was obtained in independent cytological visualization of nonmethylated CpG islands in individual human cell nuclei. CpG islands were observed to cluster in the nuclear space. The results testify that the interaction of housekeeping gene promoters is an important factor that determines the spatial organization of interphase chromosomes.