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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MeDIP of adult whole brain tissue from fetal alcohol exposed mice

ABSTRACT: In this report we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. We found long lasting alterations in DNA methylation as a result of fetal alcohol exposure, specifically in the imprinted regions of the genome harboring ncRNAs and sequences interacting with regulatory proteins. ~20% of the altered ncRNAs mapped to three imprinted regions: Snrpn-Ube3a, Dlk1-Dio3, and Sfmbt2, which showed differential methylation and have been previously implicated in neurodevelopmental disorders. The findings of this report help to expand on the mechanisms behind the long lasting changes in the brain transcriptome of FASD individuals. Comparison of fetal alcohol exposed and matched control adult C57/BL6J mice brains with olfactory bulbs removed

ORGANISM(S): Mus musculus

SUBMITTER: Benjamin Laufer

PROVIDER: E-GEOD-47111 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Long-lasting alterations to DNA methylation and ncRNAs could underlie the effects of fetal alcohol exposure in mice.

Laufer Benjamin I BI Mantha Katarzyna K Kleiber Morgan L ML Diehl Eric J EJ Addison Sean M F SM Singh Shiva M SM

Disease models & mechanisms 20130410 4

Fetal alcohol spectrum disorders (FASDs) are characterized by life-long changes in gene expression, neurodevelopment and behavior. What mechanisms initiate and maintain these changes are not known, but current research suggests a role for alcohol-induced epigenetic changes. In this study we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. W ...[more]

PMID: 23580197

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MeDIP of adult whole brain tissue from fetal alcohol exposed mice

Project description:In this report we assessed alterations to adult mouse brain tissue by assaying DNA cytosine methylation and small noncoding RNA (ncRNA) expression, specifically the microRNA (miRNA) and small nucleolar RNA (snoRNA) subtypes. We found long lasting alterations in DNA methylation as a result of fetal alcohol exposure, specifically in the imprinted regions of the genome harboring ncRNAs and sequences interacting with regulatory proteins. ~20% of the altered ncRNAs mapped to three imprinted regions: Snrpn-Ube3a, Dlk1-Dio3, and Sfmbt2, which showed differential methylation and have been previously implicated in neurodevelopmental disorders. The findings of this report help to expand on the mechanisms behind the long lasting changes in the brain transcriptome of FASD individuals.

2013-05-21 | GSE47111 | GEO

Ube3a-ATS characterization with strand-speicific microarray

Project description:This strand-specific array is performed to characterize expression features of Ube3a-ATS, including its imprinting status, its exon-intron structure, its transcriptional initiation and termination site as well as its polyadenylation status. The array contains reverse-complementary probes detecting transcripts from both strands and therefore we are able to pick up signal from both Ube3a sense and antisense. By comparing wild-type with various mutants, and total RNA with polyA RNA, we concluded that Ube3a-ATS is a paternally imprinted gene covering the whole gene body of Ube3a in the antisense orientation. It does not have an obvious exon-intron structure. Its transcription initiates at Snrpn major promoter and terminates ~40kb upstream of Ube3a transcriptional start site. Total RNA from Snrpn-Ube3a maternal deletion mutant (del s-u/+), its wild-type littermate, paternal deletion mutant and its wildtype littermate were analyzed. Mutant mice with S-U maternal deletion and Snrpn promoter paternal deleiton which leads to depletion of Ube3a-ATS (del s-u/0.9 and del s-u/4.8) were also analyzed. polyA RNA was purified from the sample 2 and sample 4. All eight samples were hybridized to the custom 8X60k Agilent CGH array.

2012-05-02 | E-GEOD-29254 | biostudies-arrayexpress

Ube3a-ATS characterization with strand-speicific microarray

2012-05-03 | GSE29254 | GEO

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Project description:Genomic imprinting is a mammalian-specific gene expression regulation system that distinguishes two parental alleles and yields parent-origin-specific gene expression. It has been identified approximately 90 imprinted gene loci in the mouse genome thus far. One of the molecular bases that establish genomic imprinting is through endogenous antisense transcription. In several imprinted loci, antisense transcription is observed in a repressive allele, probably contributing to the parent-origin-specific gene expression establishment. We investigated the allele- and strand-specific transcriptional dynamics of a megabase-wide genomic region of mouse Ube3a (ubiquitin protein ligase E3A), which is maternally expressed in a tissue-specific manner, by means of a highly parallel SNP genotyping platform that targets the tissue transcriptome. We successfully observed higher resolution transcriptional activity in the vicinity, including brain-specific widespread antisense transcription. We have listed up SNP sites within Ube3a-Snurf/Snrpn region between C57BL/6J and MSM/Ms. SNP sites were loaded onto Illumina GoldenGate Assay platform, and were assayed by targeting total RNA came from brain and liver of F1 hybrid mice.

2010-11-12 | E-GEOD-21667 | biostudies-arrayexpress

UBE3A-mediated regulation of imprinted genes and epigenome-wide marks in human neurons

Project description:The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A.Z. To understand the impact of neuronal UBE3A levels on epigenome-wide marks of DNA methylation, histone variant H2A.Z positioning, active H3K4me3 promoter marks, and gene expression, we took a multi-layered genomics approach. We performed an siRNA knockdown of UBE3A in two human neuroblastoma cell lines, including parental SH-SY5Y and the SH(15M) model of Dup15q. Genes differentially methylated across cells with differing UBE3A levels were enriched for functions in gene regulation, DNA binding, and brain morphology. Importantly, we found that altering UBE3A levels had a profound epigenetic effect on the methylation levels of up to half of known imprinted genes. Genes with differential H2A.Z peaks in SH(15M) compared to SH-SY5Y were enriched for ubiquitin and protease functions and associated with autism, hypoactivity, and energy expenditure. Together, these results support a genome-wide epigenetic consequence of altered UBE3A levels in neurons and suggest that UBE3A regulates an imprinted gene network involving DNA methylation patterning and H2A.Z deposition.

2017-09-26 | GSE103309 | GEO

Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain

Project description:Prenatal alcohol exposure is recognized to alter DNA methylation profiles of brain cells during development, and as being part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder (FASD) etiology. However, we have negligible information on the effects of alcohol during the initial embryonic stages, a window marked with dynamic DNA methylation reprogramming, and on how this may rework the brain developmental program. Using a pre-clinical in vivo mouse model, we show that pre-implantation alcohol exposure leads to adverse developmental outcomes that replicate clinical facets observed in children with FASD. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinted control regions, and abnormal re-establishment of de novo DNA methylation profiles in various biological pathways (e.g, neural/brain development). These findings support the contribution of alcohol-induced DNA methylation programming deviations during pre-implantation to the manifestations of neurodevelopmental phenotypes associated with FASD.

2023-01-17 | GSE162765 | GEO

Macro ncRNAs are abundant in imprinted regions and directly regulated by DNA methylation [tiling array]

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2017-02-25 | GSE26718 | GEO

Persistent Alterations in the imprinted miRNA and snoRNA populations in mouse models of fetal alcohol spectrum disorders (FASD)

Project description:We sought to characterize the persistnet changes in brain miRNAs across multiple mouse models of fetal alcohol exposure We used miRNA expression arrays to characterize and observe the deregulation of brain specific ncRNAs Whole brain tissue was harvested from day 70 fetal alcohol exposed males and matched controls for RNA extraction and hybridization to affymetrix miRNA 2.0 arrays. We obtained tissue from four models: Trimiester 1,2, and 3, injections and contious preference drinking.

2011-12-14 | E-GEOD-34413 | biostudies-arrayexpress

Persistent Alterations in the imprinted miRNA and snoRNA populations in mouse models of fetal alcohol spectrum disorders (FASD)

2011-12-14 | GSE34413 | GEO

Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways

Project description:UBE3A encodes a E3 ubiquitin ligase whose loss from the maternal allele causes the neurodevelopmental disorder Angelman syndrome. Previous studies of UBE3A function have not examined full Ube3a deletion in mouse, the complexity of imprinted gene networks in brain, nor the molecular basis of systems-level cognitive dysfunctions in Angelman syndrome. We therefore utilized a systems biology approach to elucidate how UBE3A loss impacts the early postnatal brain in a novel CRISPR/Cas9 engineered rat Angelman model of a complete Ube3a deletion. Strand-specific transcriptome analysis of offspring from maternally or paternally inherited Ube3a deletions revealed the expected parental expression patterns of Ube3a sense and antisense transcripts by postnatal day 2 (P2) in hypothalamus and day 9 (P9) in cortex, compared to wild-type littermates. The dependency of genome-wide effects on parent-of-origin, Ube3a genotype, and time (P2, P9) was investigated through transcriptome (RNA-seq of cortex and hypothalamus) and methylome (whole genome bisulfite sequencing of hypothalamus). Weighted gene co-expression and co-methylation network analyses identified co-regulated networks in maternally inherited Ube3a deletion offspring enriched in postnatal developmental processes including Wnt signaling, synaptic regulation, neuronal and glial functions, epigenetic regulation, ubiquitin, circadian entrainment, and splicing. Furthermore, we showed that loss of the paternal Ube3a antisense transcript resulted in both unique and overlapping dysregulated gene pathways with maternal loss, predominantly at the level of differential methylation. Together, these results provide a holistic examination of the molecular impacts of UBE3A loss in brain, supporting the existence of interactive epigenetic networks between maternal and paternal transcripts at the Ube3a locus.

2020-03-01 | GSE137217 | GEO

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