Promyelocytic Leukemia Nuclear Bodies: A Meeting Place For Genomic Loci

The nucleus is a highly compartmentalized organelle where specific cellular activities are confined to discrete domains. One such domain is the promyelocytic leukemia nuclear body (PML NB). PML NBs are protein-based structures that make numerous contacts with neighboring chromatin domains. To elucidate the function of PML NBs, research has been focused on identifying the protein complement of PML NBs. More than 60 proteins have been shown to localize to PML NBs, implicating the bodies in numerous cellular activities such as transcription regulation, apoptosis, tumor suppression, and the antiviral response. This approach has not yielded a general model for PML NB function. Instead I have chosen to focus on the chromatin contacts made with PML NBs. Using live-cell microscopy, my observations support the hypothesis that changes in chromatin topology affect the structural integrity of PML NBs. Moreover, I have developed a technique, called immunoTRAP, which allows for the extraction of chromatin specifically associated with PML NBs. Analysis of these chromatin associations reveal that specific genes associate with PML NBs and these associations are cell type specific. Therefore, PML NBs make specific contacts with neighboring chromatin domains and these contacts are integral to PML NB morphology. Thus making PML NBs a meeting place for a specific set of genomic loci.Ph