Genomic imprinting does not reduce the dosage of UBE3A in neurons
Abstract 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 neurode...
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-017-0134-4 |
| _version_ | 1819060131054223360 |
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| author | Paul R. Hillman Sarah G. B. Christian Ryan Doan Noah D. Cohen Kranti Konganti Kory Douglas Xu Wang Paul B. Samollow Scott V. Dindot |
| author_facet | Paul R. Hillman Sarah G. B. Christian Ryan Doan Noah D. Cohen Kranti Konganti Kory Douglas Xu Wang Paul B. Samollow Scott V. Dindot |
| author_sort | Paul R. Hillman |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-21T14:22:06Z |
| format | Article |
| id | doaj.art-88bdb0bfe6834033969b214ce2186bc9 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-21T14:22:06Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-88bdb0bfe6834033969b214ce2186bc92022-12-21T19:00:45ZengBMCEpigenetics & Chromatin1756-89352017-05-0110111410.1186/s13072-017-0134-4Genomic imprinting does not reduce the dosage of UBE3A in neuronsPaul R. Hillman0Sarah G. B. Christian1Ryan Doan2Noah D. Cohen3Kranti Konganti4Kory Douglas5Xu Wang6Paul B. Samollow7Scott V. Dindot8Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityInstitute for Genome Science and Society, Texas A&M UniversityDepartment of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Molecular Biology and Genetics, Cornell UniversityDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityDepartment of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversityAbstract 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.http://link.springer.com/article/10.1186/s13072-017-0134-4Ube3aGenomic imprintingDosage compensationAngelman syndromeUbe3a antisenseEvolution |
| spellingShingle | Paul R. Hillman Sarah G. B. Christian Ryan Doan Noah D. Cohen Kranti Konganti Kory Douglas Xu Wang Paul B. Samollow Scott V. Dindot Genomic imprinting does not reduce the dosage of UBE3A in neurons Epigenetics & Chromatin Ube3a Genomic imprinting Dosage compensation Angelman syndrome Ube3a antisense Evolution |
| title | Genomic imprinting does not reduce the dosage of UBE3A in neurons |
| title_full | Genomic imprinting does not reduce the dosage of UBE3A in neurons |
| title_fullStr | Genomic imprinting does not reduce the dosage of UBE3A in neurons |
| title_full_unstemmed | Genomic imprinting does not reduce the dosage of UBE3A in neurons |
| title_short | Genomic imprinting does not reduce the dosage of UBE3A in neurons |
| title_sort | genomic imprinting does not reduce the dosage of ube3a in neurons |
| topic | Ube3a Genomic imprinting Dosage compensation Angelman syndrome Ube3a antisense Evolution |
| url | http://link.springer.com/article/10.1186/s13072-017-0134-4 |
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