Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans.
Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, 'puppet-like' ataxic gait with jerky arm movements, seizures, EEG abnormalities, hyperactivity and bouts of inappropriate laughter. Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A). UBE3A is transcribed predominantly from the maternal allele in brain, but is expressed from both alleles in most other tissues. It has been proposed that brain-specific silencing of the paternal UBE3A allele is mediated by a large (>500 kb) paternal non-coding antisense transcript (UBE3A-ATS). There are several other examples of imprinting regulation involving antisense transcripts that share two main properties: (i) the sense transcript is repressed by antisense and (ii) the interaction between sense and antisense occurs in cis. We show here that, in a mouse model of AS, maternal transmission of Ube3a mutation leads to increased expression of the paternal Ube3a-ATS, suggesting that the antisense is modulated by sense rather than the reciprocal mode of regulation. Our observation that Ube3a regulates expression of Ube3a-ATS in trans is in contrast to the other cases of sense-antisense epigenetic cis-interactions and argues against a major role for Ube3a-ATS in the imprinting of Ube3a.
Landers
Miguel
M
Department of Genetics and Developmental Biology, University of Connecticut Health Center Farmington, CT 06030-3301, USA.
Calciano
Margaret A
MA
Colosi
Dan
D
Glatt-Deeley
Heather
H
Wagstaff
Joseph
J
Lalande
Marc
M
D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D005260:Female; D018392:Genomic Imprinting; D051379:Mice; D009154:Mutation; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation
D016372:RNA, Antisense; C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases