Human Molecular Genetics, 2003, Vol. 12, No. 8 837-847
DOI: 10.1093/hmg/ddg106
© 2003 Oxford University Press
Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a
1Department of Human Genetics and 2Department of Obstetrics and Gynecology, School of Medicine, Nagasaki University, Nagasaki, Japan, 3Department of Biochemistry, Saga Medical School, Saga, Japan, 4Gene Research Center, Nagasaki University, Nagasaki, Japan, 5Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, Saitama, Japan and 6Department of Pediatrics and Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, VA, USA
Received December 2, 2002; Revised February 7, 2003; Accepted February 14, 2003
The human UBE3A gene shows brain-specific partial imprinting, and lack of a maternally inherited allele causes Angelman syndrome (AS), which is characterized by neurobehavioral anomalies. In several AS model mice, imprinted Ube3a expression is detected predominantly in the hippocampus, cerebellar Purkinje cells and the olfactory bulb. Therefore, imprinting of mouse Ube3a is thought to be region-specific with different levels of silencing of the paternal Ube3a allele in different brain regions. To determine cell types of imprinted Ube3a expression, we analyzed its imprinting status in embryonic brain cells by using primary cortical cell cultures. RT–PCR and immunofluorescence were performed to determine the allelic expression of the gene. The Ube3a gene encodes two RNA transcripts in the brain, sense and antisense. The sense transcript was expressed maternally in neurons but biallelically in glial cells in the embryonic brain, whereas the antisense transcript was expressed only in neurons and only from the paternal allele. Our data present evidence of brain cell type-specific imprinting, i.e. neuron-specific imprinting of Ube3a in primary brain cell cultures. Reciprocal imprinting of sense and antisense transcripts present only in neurons suggests that the neuron-specific imprinting mechanism is related to the lineage determination of neural stem cells.
* To whom correspondence should be addressed at: Nagasaki University Gene Research Center, 1-12-4 Sakamoto-machi, Nagasaki, Japan. Tel: +81 958497120; Fax: +81 958497121; Email: kishino{at}net.nagasaki-u.ac.jp
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