Angelman syndrome imprinting center encodes a transcriptional promoter.
Clusters of imprinted genes are often controlled by an imprinting center that is necessary for allele-specific gene expression and to reprogram parent-of-origin information between generations. An imprinted domain at 15q11-q13 is responsible for both Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two clinically distinct neurodevelopmental disorders. Angelman syndrome arises from the lack of maternal contribution from the locus, whereas Prader-Willi syndrome results from the absence of paternally expressed genes. In some rare cases of PWS and AS, small deletions may lead to incorrect parent-of-origin allele identity. DNA sequences common to these deletions define a bipartite imprinting center for the AS-PWS locus. The PWS-smallest region of deletion overlap (SRO) element of the imprinting center activates expression of genes from the paternal allele. The AS-SRO element generates maternal allele identity by epigenetically inactivating the PWS-SRO in oocytes so that paternal genes are silenced on the future maternal allele. Here we have investigated functional activities of the AS-SRO, the element necessary for maternal allele identity. We find that, in humans, the AS-SRO is an oocyte-specific promoter that generates transcripts that transit the PWS-SRO. Similar upstream promoters were detected in bovine oocytes. This result is consistent with a model in which imprinting centers become DNA methylated and acquire maternal allele identity in oocytes in response to transiting transcription.
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610-0266;
Michael W
MW
Lewis
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610-0245;
Jason O
JO
Brant
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL 32610-0294; and.
Joseph M
JM
Kramer
Department of Animal Sciences, University of Florida, Gainesville, FL 32611-0910.
James I
JI
Moss
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610-0245;
Thomas P
TP
Yang
Department of Animal Sciences, University of Florida, Gainesville, FL 32611-0910.
Peter J
PJ
Hansen
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville, FL 32610-0294; and.
R Stan
RS
Williams
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610-0266; resnick@mgm.ufl.edu.
James L
JL
Resnick
D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D002417:Cattle; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D040461:Gene Components; D005786:Gene Expression Regulation / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D009865:Oocytes / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D055517:snRNP Core Proteins / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; C526417:SNRPN protein, human; D055517:snRNP Core Proteins
Angelman syndrome; imprinting; oocytes