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 chromosome 15q11-q13, exemplifies coordinate control of imprinted gene expression over a large chromosomal domain. Establishment of the paternal state of the region requires the PWS imprinting center (PWS-IC); establishment of the maternal state requires the AS-IC. Cytosine methylation of the PWS-IC, which occurs during oogenesis in mice, occurs only after fertilization in humans, so this modification cannot be the gametic imprint for the PWS/AS region in humans. Here, we demonstrate that the PWS-IC shows parent-specific complementary patterns of H3 lysine 9 (Lys9) and H3 lysine 4 (Lys4) methylation. 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 changes in chromatin packaging during the life cycle of mammals provide a means of erasing such an imprint in the male germline.
Xin
Z
Z
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA, USA.
Allis
C D
CD
Wagstaff
J
J
D000483:Alleles; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D019175:DNA Methylation; D005091:Exons / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008957:Models, Genetic; D011218:Prader-Willi Syndrome / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
D006657:Histones; D008239:Lysine