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Epigenomics. 2015 Oct;7(7):1213-28. doi: 10.2217/epi.15.70. Epub 2015 Nov 20.

Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders.

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Medical Microbiology & Immunology, Genome Center & MIND Institute, University of California, Davis, CA 95616, USA.
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Department of Genetics & Developmental Biology & Stem Cell Institute, University of Connecticut, Farmington, CT 06030, USA.


The E3 ubiquitin ligase UBE3A, also known as E6-AP, has a multitude of ascribed functions and targets relevant to human health and disease. Epigenetic regulation of the UBE3A gene by parentally imprinted noncoding transcription within human chromosome 15q11.2-q13.3 is responsible for the maternal-specific effects of 15q11.2-q13.3 deletion or duplication disorders. Here, we review the evidence for diverse and emerging roles for UBE3A in the proteasome, synapse and nucleus in regulating protein stability and transcription as well as the current mechanistic understanding of UBE3A imprinting in neurons. Angelman and Dup15q syndromes as well as experimental models of these neurodevelopmental disorders are highlighted as improving understanding of UBE3A and its complex regulation for improving therapeutic strategies.


Angelman syndrome; Dup15q syndrome; imprinting; neurodevelopment; proteosome; ubiquitin

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Financial & competing interests disclosure The authors thank the NIH NINDS (R01NS076263) and the Prader–Willi Research Foundation for ongoing support of research in this area. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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