دورية أكاديمية
Influence of the Prader-Willi syndrome imprinting center on the DNA methylation landscape in the mouse brain.
العنوان: | Influence of the Prader-Willi syndrome imprinting center on the DNA methylation landscape in the mouse brain. |
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المؤلفون: | Brant JO; a Department of Biochemistry and Molecular Biology ; University of Florida ; Gainesville , FL USA., Riva A, Resnick JL, Yang TP |
المصدر: | Epigenetics [Epigenetics] 2014 Nov; Vol. 9 (11), pp. 1540-56. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101265293 Publication Model: Print Cited Medium: Internet ISSN: 1559-2308 (Electronic) Linking ISSN: 15592294 NLM ISO Abbreviation: Epigenetics Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Georgetown, Tex. : Landes Bioscience, c2006- |
مواضيع طبية MeSH: | DNA Methylation* , Genomic Imprinting*, Brain/*physiology , Prader-Willi Syndrome/*genetics, Angelman Syndrome/genetics ; Animals ; Antigens, Neoplasm/genetics ; Carrier Proteins/genetics ; CpG Islands ; Female ; High-Throughput Nucleotide Sequencing ; Male ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neoplasm Proteins/genetics ; Promoter Regions, Genetic ; Proteins/genetics ; Ribonucleoproteins/genetics ; Sequence Deletion ; Ubiquitin-Protein Ligases |
مستخلص: | Reduced representation bisulfite sequencing (RRBS) was used to analyze DNA methylation patterns across the mouse brain genome in mice carrying a deletion of the Prader-Willi syndrome imprinting center (PWS-IC) on either the maternally- or paternally-inherited chromosome. Within the ~3.7 Mb imprinted Angelman/Prader-Willi syndrome (AS/PWS) domain, 254 CpG sites were interrogated for changes in methylation due to PWS-IC deletion. Paternally-inherited deletion of the PWS-IC increased methylation levels ~2-fold at each CpG site (compared to wild-type controls) at differentially methylated regions (DMRs) associated with 5' CpG island promoters of paternally-expressed genes; these methylation changes extended, to a variable degree, into the adjacent CpG island shores. Maternal PWS-IC deletion yielded little or no changes in methylation at these DMRs, and methylation of CpG sites outside of promoter DMRs also was unchanged upon maternal or paternal PWS-IC deletion. Using stringent ascertainment criteria, ~750,000 additional CpG sites were also interrogated across the entire mouse genome. This analysis identified 26 loci outside of the imprinted AS/PWS domain showing altered DNA methylation levels of ≥25% upon PWS-IC deletion. Curiously, altered methylation at 9 of these loci was a consequence of maternal PWS-IC deletion (maternal PWS-IC deletion by itself is not known to be associated with a phenotype in either humans or mice), and 10 of these loci exhibited the same changes in methylation irrespective of the parental origin of the PWS-IC deletion. These results suggest that the PWS-IC may affect DNA methylation at these loci by directly interacting with them, or may affect methylation at these loci through indirect downstream effects due to PWS-IC deletion. They further suggest the PWS-IC may have a previously uncharacterized function outside of the imprinted AS/PWS domain. |
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معلومات مُعتمدة: | R01 NS086456 United States NS NINDS NIH HHS; R01 HD057026 United States HD NICHD NIH HHS |
فهرسة مساهمة: | Keywords: AS, Angelman Syndrome; AS-IC, Angelman Syndrome Imprinting Center; AS-SRO, Angelman Syndrome Shortest Region of deletion Overlap; BGS, Sodium Bisulfite Genomic Sequencing; BISSCA, Bisulfite Sequencing Comparative Analysis; CGI, CpG Island; DH, DNase I Hypersensitive; DMR, Differentially Methylated Region; DNA methylation; EtOH, Ethanol; GO, gene ontology; IC, Imprinting Center; ICR, Imprinting Control Region; IPA, Ingenuity Pathway Analysis ®; PWS, Prader-Willi Syndrome; PWS-IC, Prader-Willi Syndrome Imprinting Center; PWS-SRO, Prader-Willi Syndrome Shortest Region of deletion Overlap; RRBS, Reduced Representation Bisulfite Sequencing; SDS, Sodium Dodecyl Sulfate; SLIM, Sliding Linear Model; TBE, Tris/Borate/EDTA; Tris, Trisaminomethane; UTR, untranslated region; angelman syndrome; genomic imprinting; imprinting center; lncRNA, long non-coding RNA; mat, maternally-inherited allele; pat, paternally-inherited allele; prader-Willi syndrome; reduced representation bisulfite sequencing |
سلسلة جزيئية: | SRA SRP038725 |
المشرفين على المادة: | 0 (Antigens, Neoplasm) 0 (Carrier Proteins) 0 (Magel2 protein, mouse) 0 (Neoplasm Proteins) 0 (Peg12 protein, mouse) 0 (Proteins) 0 (Ribonucleoproteins) EC 2.3.2.27 (Mkrn3 protein, mouse) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
تواريخ الأحداث: | Date Created: 20141209 Date Completed: 20150803 Latest Revision: 20240324 |
رمز التحديث: | 20240324 |
مُعرف محوري في PubMed: | PMC4623435 |
DOI: | 10.4161/15592294.2014.969667 |
PMID: | 25482058 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1559-2308 |
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DOI: | 10.4161/15592294.2014.969667 |