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

Am J Hum Genet. 2001 Dec;69(6):1389-94. doi: 10.1086/324469. Epub 2001 Oct 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 15 / genetics*
  • DNA Methylation*
  • Exons / genetics
  • Female
  • Genomic Imprinting / genetics*
  • Germ Cells / metabolism
  • Histones / chemistry*
  • Histones / genetics*
  • Humans
  • Lysine / genetics
  • Lysine / metabolism*
  • Male
  • Models, Genetic
  • Prader-Willi Syndrome / genetics*
  • Prader-Willi Syndrome / metabolism
  • Promoter Regions, Genetic / genetics


  • Histones
  • Lysine