IDENTIFICATION OF A SILENCING ELEMENT IN THE HUMAN 15Q11-Q13 IMPRINTING CENTER BY USING TRANSGENIC DROSOPHILA

Prader-Willi syndrome (PWS) and Angelman syndrome are neurogenetic dis orders caused by the lack of a paternal or a maternal contribution fro m human chromosome 15q11-q13, respectively, Deletions in the transcrip tion unit of the imprinted SNRPN gene have been found in patients who have PWS or Angelman syndrome because of a parental imprint switch fai lure in this chromosomal domain, It has been suggested that the SNRPN exon 1 region, which is deleted in the PWS patients, contains an impri nt switch element from which the maternal and paternal epigenotypes of the 15q11-q13 domain originate, Using the model organism Drosophila, we show here that a fragment from this region can function as a silenc er in transgenic flies, Repression was detected specifically from this element and could not be observed with control human sequences, Addit ional experiments allowed the delineation of the silencer to a fragmen t of 215 bp containing the SNRPN promoter region, These results provid e an additional link between genomic imprinting and an evolutionary co nserved silencing mechanism, We suggest that the identified element pa rticipates in the long range relation of the imprinted 15q11-q13 domai n or locally represses SNRPN expression from the maternal allele.