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Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin-dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.

The Human Imprintome: Regulatory Mechanisms, Methods of Ascertainment, and Roles in Disease Susceptibility