Stefan H. Stricker Reprogramming and Regeneration, Biomedical Center (BMC), Physiological Genomics, Faculty of Medicine, Ludwig Maximilian University (LMU) Munich, Planegg-Martinsried 82152, Germany; Epigenetic Epigenetic Engineering, Institute of Stem Cell Research, Helmholtz Zentrum, German Research Center for Environmental Health, Planegg-Martinsried 82152, Germany Corresponding author: stefan.strickerhelmholtz-muenchen.de Abstract

Imprinted gene clusters are confined genomic regions containing genes with parent-of-origin-dependent transcriptional activity. In this issue of Genes & Development, Loftus and colleagues (pp. 829–843) made use of an insightful combination of descriptive approaches, genetic manipulations, and epigenome-editing approaches to show that differences in nuclear topology precede the onset of imprinted expression at the Peg13-Kcnk9 locus. Furthermore, the investigators provide data in line with a model suggesting that parent-of-origin-specific topological differences could be responsible for parent-of-origin-specific enhancer activity and thus imprinted expression.