The imprinting box of the Prader-Willi/Angelman syndrome domain

Ruth Shemer, Alon Y. Hershko, Jonathan Perk, Raul Mostoslavsky, Ben Zion Tsuberi, Howard Cedar, Karin Buiting, Aharon Razin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


A subset of mammalian genes is monoallelically expressed in a parent-of-origin manner. These genes are subject to an imprinting process that epigenetically marks alleles according to their parental origin during gametogenesis. Imprinted genes can be organized in clusters as exemplified by the 2-Mb domain on human chromosome 15q11-q13 and its mouse orthologue on chromosome 7c (ref. 1). Loss of this 2-Mb domain on the paternal or maternal allele results in two neurogenetic disorders, Prader-Wile syndrome (PWS) or Angelman syndrome (AS), respectively. Microdeletions on the paternal allele share a 4.3-kb short region of overlap (SRO), which includes the SNRPN promoter/exon1, cause PWS and silence paternally expressed genes. Microdeletions on the maternal allele share a 0.88-kb SRO located 35 kb upstream to the SNRPN promoter, cause AS and alleviate repression of genes on the maternal allele. Individuals carrying both AS and PWS deletions on the paternal allele show a PWS phenotype and genotype. These observations suggest that cis elements within the AS-SRO and PWS-SRO constitute an imprinting box that regulates the entire domain on both chromosomes. Here we show that a minitransgene composed of a 200-bp Snrpn promoter/exon1 and a 1-kb sequence located approximately 35 kb upstream to the SNRPN promoter confer imprinting as judged by differential methylation, parent-of-origin-specific transcription and asynchronous replication.

Original languageAmerican English
Pages (from-to)440-443
Number of pages4
JournalNature Genetics
Issue number4
StatePublished - 2000

Bibliographical note

Funding Information:
We thank B. Horsthemke for comments. The work was supported by the Israel Science Foundation-Centers of Excellence Program, the NIH (A.R. and H.C.), the Israel Ministry of Health (A.R. and R.S.) and the US–Israel Binational Science Foundation (H.C.). A.Y.H. was partially supported by a Foulkes Foundation fellowship.


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