Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain

Vu, Thanh H.; Hoffman, Andrew R.

doi:10.1038/ng0997-12

Cited by 282 publications

(162 citation statements)

References 7 publications

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“…Imprinting of this gene is maintained in discrete regions of the adult brain (Albrecht et al 1997;Rougeulle et al 1997;Vu & Hoffman 1997), and as we have seen previously, this gene is involved in aspects of social functioning in the young (Oliver et al 2002), so may well have a similar function in the adult. This idea is supported by the fact that UBE3A has been implicated in autismspectrum disorders (Cook et al 1997;Samaco et al 2005).…”

Section: Sex-biased Dispersal Intragenomic Conflict and Social Behavmentioning

confidence: 77%

Genomic imprinting and the social brain

Isles

Davies

Wilkinson

2006

Phil. Trans. R. Soc. B

108

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Genomic imprinting refers to the parent-of-origin-specific epigenetic marking of a number of genes. This epigenetic mark leads to a bias in expression between maternally and paternally inherited imprinted genes, that in some cases results in monoallelic expression from one parental allele. Genomic imprinting is often thought to have evolved as a consequence of the intragenomic conflict between the parental alleles that occurs whenever there is an asymmetry of relatedness. The two main examples of asymmetry of relatedness are when there is partiality of parental investment in offspring (as is the case for placental mammals, where there is also the possibility of extended postnatal care by one parent), and in social groups where there is a sex-biased dispersal. From this evolutionary starting point, it is predicted that, at the behavioural level, imprinted genes will influence what can broadly be termed bonding and social behaviour. We examine the animal and human literature for examples of imprinted genes mediating these behaviours, and divide them into two general classes. Firstly, mother-offspring interactions (suckling, attachment and maternal behaviours) that are predicted to occur when partiality in parental investment in early postnatal offspring occurs; and secondly, adult social interactions, when there is an asymmetry of relatedness in social groups. Finally, we return to the evolutionary theory and examine whether there is a pattern of behavioural functions mediated by imprinted genes emerging from the limited data, and also whether any tangible predictions can be made with regards to the direction of action of genes of maternal or paternal origin.

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Section: Sex-biased Dispersal Intragenomic Conflict and Social Behavmentioning

confidence: 77%

Genomic imprinting and the social brain

Isles

Davies

Wilkinson

2006

Phil. Trans. R. Soc. B

108

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“…85,86 UBE3A displays predominant maternal expression in human fetal brain and adult frontal cortex. [87][88][89] In mouse, maternal allele-specific expression is detected in specific brain subregions including hippocampus, cerebellum, olfactory bulb, and visual cortex. 83,84,90 Other brain regions may also show this type of allele-specific expression.…”

Section: Ubiquitin Ligase E3a (Ube3a)mentioning

confidence: 99%

“…UBE3A spans approximately 120 kb of genomic DNA and contains 16 exons. The 5Ј untranslated region (UTR) extends several kilobases upstream from the initiation site and spans an additional six to nine exons, 65,89,95,96 whereas the 3Ј UTR extends an additional 2.0 kb. 95 To date, alternative splicing of the 5Ј UTR accounts for the production of nine adult and two fetal transcripts, 65,89,95,96 which are translated into three different protein isoforms.…”

Section: Ubiquitin Ligase E3a (Ube3a)mentioning

confidence: 99%

Clinical and genetic aspects of Angelman syndrome

Williams

Driscoll

Dagli

2010

Genetics in Medicine

268

235

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“…UBE3A protein is primarily expressed by the maternal allele in mature neurons, due to evolutionarily conserved, tissue-specific mechanisms of imprinting (Rougeulle et al, 1997;Vu and Hoffman, 1997). Mouse models of AS carry maternally-inherited Ube3a deletions, and display many Angelman-like phenotypes, including learning and memory deficits, motor dysfunction, and seizures (Jiang et al, 1998;Miura et al, 2002;van Woerden et al, 2007;Heck et al, 2008;Jiang et al, 2010;Mulherkar and Jana, 2010;Margolis et al, 2015).…”

Section: Hhs Public Accessmentioning

confidence: 99%

Subcellular organization of UBE3A in neurons

Burette

Judson

Burette

et al. 2016

J of Comparative Neurology

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Ubiquitination regulates a broad array of cellular processes, and defective ubiquitination is implicated in several neurological disorders. Loss of the E3 ubiquitin-protein ligase UBE3A causes Angelman syndrome. Despite its clinical importance, the normal role of UBE3A in neurons is still unclear. As a step toward deciphering its possible functions, we performed high-resolution light and electron microscopic immunocytochemistry. We report a broad distribution of UBE3A in neurons, highlighted by concentrations in axon terminals and euchromatin-rich nuclear domains. Our findings suggest that UBE3A may act locally to regulate individual synapses, while also mediating global, neuron-wide influences through the regulation of gene transcription. KeywordsAngelman syndrome; E6-AP; ubiquitin-proteasome pathway; axon terminal; mitochondria; euchromatin; heterochromatin; RRID:nif-0000-30467; RRID:AB_10740376The ubiquitin-proteasome pathway, which provides a mechanism for protein degradation in eukaryotes, is important for a broad array of basic cellular processes. Neurons have long dendrites and axons whose distal regions are remote from the soma, emphasizing the importance of local protein synthesis and degradation in neuronal function. Accordingly, the ubiquitin-proteasome pathways has been shown to be important for appropriate circuit wiring, neuronal morphogenesis, intracellular trafficking, and synaptic plasticity (Hegde, * Correspondence to: Benjamin D. Philpot, bphilpot@med.unc.edu, Richard J. Weinberg, richard.weinberg@gmail.com. Conflict of interest statementAuthors verify that they have no known or potential conflict of interest including any financial, personal, or other relationships with other people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, this work. 2004;Acconcia et al., 2009;Cajigas et al., 2010;Schwarz and Patrick, 2012;Hamilton and Zito, 2013;Goo et al., 2015). Conversely, dysregulation of the ubiquitin-proteasome system has been implicated in multiple neurological disorders including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and autism (Tai and Schuman, 2008;Schwarz and Patrick, 2012). HHS Public AccessThe covalent attachment of ubiquitin to protein substrates involves sequential reactions catalyzed by a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin-protein ligase (E3). The E3 ligases largely dictate specificity and target protein recognition for the ubiquitin conjugation system; thus the biology of E3 ligases is of broad biological and clinical importance. Based on their distinct domains and mode of action, E3 proteins segregate into three families: RING/RING-like E3s, RING-in-between-RING (RBR) E3s, and Homologous to the E6-AP Carboxyl Terminus (HECT) E3s. The loss of expression or function of UBE3A (also called E6-AP), the founding member of the HECT E3 ligase family, leads to Angelman syndrome (AS), a severe n...

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Imprinting of the Angelman syndrome gene, UBE3A, is restricted to brain

Cited by 282 publications

References 7 publications

Genomic imprinting and the social brain

Genomic imprinting and the social brain

Clinical and genetic aspects of Angelman syndrome

Subcellular organization of UBE3A in neurons

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