The architectural organization of the nucleus is poorly understood. However, some active genes are repartitioned from the interior to the periphery of nuclear territories. “A number of studies have shown that there are interchromosomal interactions that provide a novel control mechanism to regulate gene expression,” noted Xiang-Dong Fu, professor, medicine/cellular and molecular medicine, University of California at San Diego (UCSD).
“New and intriguing questions have emerged from the recent genome-wide analyses of DNA binding sites for transcription factors,” explained Dr. Fu. “We see that there can be numerous remote chromosomal binding sites that communicate with their putative target genes by long-distance intrachromosomal and likely interchromosomal interactions.”
Dr. Fu and his collaborator, Michael G. Rosenfeld, M.D., an investigator for the Howard Hughes Medical Institute at UCSD, are working to define how such interactions take place. Their studies target genes regulated by nuclear receptors such as the estrogen receptor. “Our groups found 17β-estradiol(E2)-induced interactions between gene loci located in different chromosomes, in particular the TFF1 gene on chromosome 21 and the GREB1 gene on chromosome 2,” Dr. Fu reports.
Using fluorescence in situ hybridization, Drs. Fu and Rosenfeld found that these interchromosomal interactions appear to be mediated by a nuclear motor system. Dr. Fu added, “this is still poorly understood at this point, but it’s important to note that these gene-gene interactions are closely correlated with enhanced gene expression in response to hormones.”
Drs. Fu and Rosenfeld also determined that the interchromosomal interactions occurred in hubs called interchromatin granules. “These granules, also called nuclear speckles, are enriched with several key transcriptional elongation factors, chromatin remodeling complexes, and essentially all factors needed for pre-mRNA splicing.”
These findings underscore the ability of chromosomes to move to and interact at these common hubs, Dr. Fu noted. “For hormone-induced genes, such interchromosomal interactions in the interchromatin granules may play an important role to coordinate and enhance regulated gene expression by allowing efficient coupling of transcriptional initiation, elongation, and RNA-processing events.”