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.

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Datasets Mentioned

BETA
ERP000591
E-MTAB-1733

Methods Mentioned

BETA
RNA-seq
PCR
Assay

Related Concepts

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

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