Abstract
Genomic imprinting describes the monoallelic and parent-of-origin dependent expression of more than 100 human genes. Molecularly, the phenomenon of genomic imprinting is based on epigenetic mechanisms and, therefore, comprises regulation by DNA modifications (e.g., 5-methylcytosine), non-coding RNAs (ncRNA) and chromatin structuring (e.g., by histone modifications). Imprinted genes tend to cluster, and each cluster is regulated by at least one differentially methylated region (DMR). Imprinted regions often harbor several DMRs, and these DMRs are then organized hierarchically with a germline DMR (gDMR) as the key regulator and subordinated somatic DMRs. An example is the imprinted region in 14q32 with the MEG3/DLK1:IG-DMR as the gDMR and the subordinated MEG3:TSS-DMR and MEG8:Int2-DMR. As this hierarchical organisation requires a balanced regulation, it is not surprising that the fine-tuned expression of imprinted genes is the prerequisite of proper development, and its disturbance has a severe impact on the phenotype.
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