Spatial organization of housekeeping genes in interphase nuclei

Abstract

Spatial organization of the eukaryotic genome is tightly connected to its functioning. In particular, the interaction of gene promoters with remote enhancer elements in active chromatin hubs, as well as the recruitment of genes to the common transcription factories plays an important role in regulation of gene transcription. Most of works related to the analysis of spatial interaction of genome regulatory elements relies on models of tissue-specific genes. Meanwhile, it remains unclear to which extent the spatial organization of chromosomes is guided by house-keeping genes that are transcribed in most of cell types and outnumber the transcribed tissue-specific genes. To address this question, we used the 4C technique to characterize genome-wide the spatial contacts of the chicken house-keeping genes CARHSP1 and TRAP1 situated on chromosome 14. The promoters of these genes had an increased frequency of interaction with chromosome regions enriched in CpG islands and binding motifs for the ubiquitous transcription factor Sp1, both of which mark promoters of house-keeping genes, and overall with transcriptionally active regions. By contrast, the analysis of interaction of a gene poor region of chromosome 14 revealed no such preferences. The evidence for the interaction of house-keeping gene promoters were also obtained in independent cytological experiments aimed at visualization of non-methylated CpG islands in individual nuclei of human cells, which showed clustering of CpG islands in the nuclear space. Altogether, the results of our work suggest that the interaction of house-keeping genes constitutes an important factor that determines the spatial organization of interphase chromosomes.