Human Cytomegalovirus (HCMV), a β-herpesvirus, is a widespread human pathogen. While for most individuals the initial infection will go unnoticed, the majority of these individuals will carry latent HCMV in specific cell populations for life. These latent viral genomes are maintained passively by the host cell and have the potential to reactivate, leading to severe morbidity and mortality for immunocompromised individuals. To date, understanding of host-virus interactions leading to long-term, yet reversible, transcriptional silencing of HCMV genes remains primitive. Direction on how this gene repression may occur to initiate and maintain HCMV latency can be drawn from latency studies done with other herpesviruses, where recent data suggests a role for Polycomb repressive complexes (PRCs) in viral gene silencing. PRCs exist in two major, multi-protein, effector complexes termed PRC1 and PRC2. Together these two complexes silence gene expression though modification of chromatin structure, rendering targeted regions refractory for transcription. PRC mediated transcriptional silencing provides an attractive mechanism for viral gene repression as it is reversible, providing the virus transcriptional potential. My work is two-fold, first, to define PRC occupancy at viral DNA sequences, and second, to demonstrate a functional interplay between PRCs and CMV genomes leading to changes in viral gene expression, ultimately influencing whether a lytic or latent infection is established.