Parent-specific complementary patterns of histone H3 lysine 9 and H3 lysine 4 methylation at the Prader-Willi syndrome imprinting center

The Prader-Willi syndrome (PWS)/Angelman syndrome (AS) region, on human chr omosome 15q11-q13, exemplifies coordinate control of imprinted gene express ion over a large chromosomal domain. Establishment of the paternal state of the region requires the PWS imprinting center (PWS-IC); establishment of t he maternal state requires the AS-IC. Cytosine methylation of the PWS-IC, w hich occurs during oogenesis in mice, occurs only after fertilization in hu mans, so this modification cannot be the gametic imprint for the PWS/AS reg ion in humans. Here, we demonstrate that the PWS-IC shows parent-specific c omplementary patterns of H3 lysine 9 (Lys9) and H3 lysine 4 (Lys4) methylat ion. H3 Lys9 is methylated on the maternal copy of the PWS-IC, and H3 Lys4 is methylated on the paternal copy. We suggest that H3 Lys9 methylation is a candidate maternal gametic imprint for this region, and we show how chang es in chromatin packaging during the life cycle of mammals provide a means of erasing such an imprint in the male germline.