Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a

Abstract

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.

LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia

“…We found that human LRRTM1 is imprinted (paternal-only expression) in hybrid A9 cells 24 (mouse cell lines containing single human chromosomes of known parental origin) ( Figure 2). Despite certain limitations with hybrid cells in the 27 ). We also found mono-allelic paternal expression of LRRTM1 in four out of four unrelated EBV-transformed human lymphoblastoid cell lines that were heterozygous for a transcribed SNP (Figure 2).…”

Clinical and genetic aspects of Angelman syndrome

“…Primary cell cultures from fetal mouse brain reveal that UBE3A imprinting is limited to neurons and that glial cells show biallelic expression. 91 There is preferential maternal expression of UBE3A in lymphoblasts and fibroblasts but the differential expression between the parental alleles is not as striking as it is in brain. 92 UBE3A has a large 5Ј CpG island but its DNA methylation does not differ between the maternal and paternal alleles.…”

Epigenetic alteration of imprinted genes during neural differentiation of germline-derived pluripotent stem cells

“…However, it has been reported that Ube3a expression is cell type-specific in the brain and that Ube3a is expressed from both parental alleles in neural progenitor cells and glial cells, which can explain the expression of Ube3a in gPSNSCs and astrocytes differentiated from gPS-NSCs. 21 Nonetheless, it is still unclear why Ube3a expression in androgenetic cells was higher than in biparental cells.…”