Genomic imprinting does not reduce the dosage of UBE3A in neurons
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 neurodevelopmen...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433054/ https://www.ncbi.nlm.nih.gov/pubmed/28515788 http://dx.doi.org/10.1186/s13072-017-0134-4 |
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author | Hillman, Paul R. Christian, Sarah G. B. Doan, Ryan Cohen, Noah D. Konganti, Kranti Douglas, Kory Wang, Xu Samollow, Paul B. Dindot, Scott V. |
author_facet | Hillman, Paul R. Christian, Sarah G. B. Doan, Ryan Cohen, Noah D. Konganti, Kranti Douglas, Kory Wang, Xu Samollow, Paul B. Dindot, Scott V. |
author_sort | Hillman, Paul R. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-017-0134-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5433054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-54330542017-05-17 Genomic imprinting does not reduce the dosage of UBE3A in neurons Hillman, Paul R. Christian, Sarah G. B. Doan, Ryan Cohen, Noah D. Konganti, Kranti Douglas, Kory Wang, Xu Samollow, Paul B. Dindot, Scott V. Epigenetics Chromatin Research 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-017-0134-4) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-15 /pmc/articles/PMC5433054/ /pubmed/28515788 http://dx.doi.org/10.1186/s13072-017-0134-4 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hillman, Paul R. Christian, Sarah G. B. Doan, Ryan Cohen, Noah D. Konganti, Kranti Douglas, Kory Wang, Xu Samollow, Paul B. Dindot, Scott V. Genomic imprinting does not reduce the dosage of UBE3A in neurons |
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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433054/ https://www.ncbi.nlm.nih.gov/pubmed/28515788 http://dx.doi.org/10.1186/s13072-017-0134-4 |
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