| First Author | Hillman PR | Year | 2017 |
| Journal | Epigenetics Chromatin | Volume | 10 |
| Pages | 27 | PubMed ID | 28515788 |
| Mgi Jnum | J:315847 | Mgi Id | MGI:6832001 |
| Doi | 10.1186/s13072-017-0134-4 | Citation | Hillman PR, et al. (2017) Genomic imprinting does not reduce the dosage of UBE3A in neurons. Epigenetics Chromatin 10:27 |
| abstractText | BACKGROUND: The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types. Both loss-of-function and gain-of-function mutations affecting the dosage of UBE3A are associated with several neurodevelopmental syndromes and psychological conditions, suggesting that UBE3A is dosage-sensitive in the brain. The observation that loss of imprinting increases the dosage of UBE3A in brain further suggests that inactivation of the paternal UBE3A allele evolved as a dosage-regulating mechanism. To test this hypothesis, we examined UBE3A transcript and protein levels among cells, tissues, and species with different imprinting states of UBE3A. RESULTS: Overall, we found no correlation between the imprinting status and dosage of UBE3A. Importantly, we found that maternal Ube3a protein levels increase in step with decreasing paternal Ube3a protein levels during neurogenesis in mouse, fully compensating for loss of expression of the paternal Ube3a allele in neurons. CONCLUSIONS: Based on our findings, we propose that imprinting of UBE3A does not function to reduce the dosage of UBE3A in neurons but rather to regulate some other, as yet unknown, aspect of gene expression or protein function. |
