The imprinting mechanism of the Prader-Willi/Angelman regional control center

Jonathan Perk, Kirill Makedonski, Laura Lande, Howard Cedar, Aharon Razin*, Ruth Shemer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

The 2 Mb domain on chromosome 15q11-q13 that carries the imprinted genes involved in Prader-Willi (PWS) and Angelman (AS) syndromes is under the control of an imprinting center comprising two regulatory regions, the PWS-SRO located around the SNRPN promoter and the AS-SRO located 35 kb upstream. Here we describe the results of an analysis of the epigenetic features of these two sequences and their interaction. The AS-SRO is sensitive to DNase I, and packaged with acetylated histone H4 and methylated histone H3(K4) only on the maternal allele, and this imprinted epigenetic structure is maintained in dividing cells despite the absence of clearcut differential DNA methylation. Genetic analysis shows that the maternal AS-SRO is essential for setting up the DNA methylation state and closed chromatin structure of the neighboring PWS-SRO. In contrast, the PWS-SRO has no influence on the epigenetic features of the AS-SRO. These results suggest a stepwise, unidirectional program in which structural imprinting at the AS-SRO brings about allele-specific repression of the maternal PWS-SRO, thereby preventing regional activation of genes on this allele.

Original languageAmerican English
Pages (from-to)5807-5814
Number of pages8
JournalEMBO Journal
Volume21
Issue number21
DOIs
StatePublished - 1 Nov 2002

Keywords

  • Angelman regional control center
  • DNA methylation
  • DNase sensitivity
  • Histone modification
  • Prader-Willi

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