Genomic imprinting does not reduce the dosage of UBE3A in neurons

Epigenetics & Chromatin
Paul R HillmanScott V Dindot


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 paternalUBE3Aallele evolved as a dosage-regulating mechanism. To test this hypothesis, we examinedUBE3Atranscript and protein levels among cells, tissues, and species with different imprinting states ofUBE3A. 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 paternalUbe3aallele in neurons. Based on our findings, we propose that imprinting ofUBE3Adoes not function to reduce the dosage ofUBE3Ain neurons but rather to regulate some other, as yet unknown, aspect of gene expression or protein function.


Jun 7, 1992·Journal of Theoretical Biology·D Haig
Aug 1, 1991·Current Opinion in Genetics & Development·M A Surani
Feb 1, 1991·Trends in Genetics : TIG·T Moore, David Haig
Jan 1, 1988·Annual Review of Genetics·D Solter
Jan 1, 1997·Nature Genetics·T KishinoJoseph Wagstaff
Sep 1, 1997·Nature Genetics·Claire RougeulleMarc Lalande
Dec 24, 1997·Proceedings. Biological Sciences·David Haig
Aug 11, 2001·Science·A C Ferguson-Smith, M A Surani
Apr 5, 2002·Advances in Genetics·Célia BarouxUeli Grossniklaus
May 3, 2003·Nature Reviews. Genetics·Jon F Wilkins, David Haig
Jul 19, 2003·Journal of Biochemistry·Tomoko Kaneko-IshinoFumitoshi Ishino
Dec 1, 2004·Annual Review of Genetics·David Haig
Feb 14, 2006·American Journal of Medical Genetics. Part a·Charles A WilliamsJoseph Wagstaff
Sep 26, 2006·Gene·Dan C ColosiMarc Lalande
Oct 31, 2006·PLoS Genetics·Robert W RapkinsJennifer A Marshall Graves
May 31, 2008·BMC Evolutionary Biology·Eleanor I AgerMarilyn B Renfree
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Aug 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yaning WuJanice A Fischer
Oct 9, 2008·Neurobiology of Disease·Amber HogartN Carolyn Schanen
May 1, 2009·Nature·Joseph T GlessnerHakon Hakonarson
Jun 27, 2009·Annual Review of Neuroscience·Arnold Kriegstein, Arturo Alvarez-Buylla
Oct 12, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Mary J O'ConnellCharles Spillane
Sep 17, 2011·Nature·Thomas M KeaneDavid J Adams
Feb 14, 2012·Cell Metabolism·Marika CharalambousA C Ferguson-Smith
Jul 13, 2012·Molecular Biology and Evolution·Jessica M StringerMarilyn B Renfree
Nov 21, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Marilyn B RenfreeTomoko Kaneko-Ishino
Dec 24, 2013·Human Molecular Genetics·Kristen Martins-TaylorStormy J Chamberlain
Jan 9, 2014·Heredity·H G Spencer, A G Clark
Sep 24, 2014·Scientific Reports·Chenna R GalivetiTimofey S Rozhdestvensky
Apr 14, 2015·Nature Neuroscience·Jeremy ValluyGerhard Schratt
May 4, 2015·Biochemical and Biophysical Research Communications·Moumita ChakrabortySupriya Bhutani
May 9, 2015·Genome Research·Yael BaranTuuli Lappalainen
Nov 21, 2015·Epigenomics·Janine M LaSalleStormy J Chamberlain
Dec 24, 2015·Genome Biology·Peter H SudmantChristopher B Burge
Mar 19, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jon F WilkinsJeremy Van Cleve
Jul 2, 2016·Clinical Genetics·L SoellnerT Eggermann
Sep 7, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Kevin A HopeLawrence T Reiter

Datasets Mentioned


Methods Mentioned


Related Concepts

Ube3a protein, mouse
Maternal Inheritance
Antisense RNA
Genomic Imprinting
Gene Dosage
Ubiquitin-protein ligase
Mouse, Swiss

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.