Genomic imprinting does not reduce the dosage of UBE3A in neurons

Epigenetics & Chromatin
Paul R HillmanScott V Dindot

Abstract

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.

References

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, D Haig
Jan 1, 1988·Annual Review of Genetics·D Solter
Jan 1, 1997·Nature Genetics·T KishinoJ Wagstaff
Sep 1, 1997·Nature Genetics·C RougeulleM Lalande
Dec 24, 1997·Proceedings. Biological Sciences·D 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 CharalambousAnne 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

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Citations

Dec 24, 2019·Journal of Neuroscience Research·Xin Yang
Jan 29, 2019·Frontiers in Molecular Neuroscience·Simon Jesse LopezJanine M LaSalle
Sep 17, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Nycole A CoppingJill L Silverman

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Datasets Mentioned

BETA
ERP000591
E-MTAB-1733

Methods Mentioned

BETA
RNA-seq
PCR
Assay

Software Mentioned

CLC Genomics Workbench
ImageJ
JMP Pro
Plot Profile
Adobe Illustrator
TopHat

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