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The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome
- Source :
- Nature Genetics. 46:551-557
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
Abstract
- Parental imprinting is a form of epigenetic regulation that results in parent-of-origin differential gene expression. To study Prader-Willi syndrome (PWS), a developmental imprinting disorder, we generated case-derived induced pluripotent stem cells (iPSCs) harboring distinct aberrations in the affected region on chromosome 15. In studying PWS-iPSCs and human parthenogenetic iPSCs, we unexpectedly found substantial upregulation of virtually all maternally expressed genes (MEGs) in the imprinted DLK1-DIO3 locus on chromosome 14. Subsequently, we determined that IPW, a long noncoding RNA in the critical region of the PWS locus, is a regulator of the DLK1-DIO3 region, as its overexpression in PWS and parthenogenetic iPSCs resulted in downregulation of MEGs in this locus. We further show that gene expression changes in the DLK1-DIO3 region coincide with chromatin modifications rather than DNA methylation levels. Our results suggest that a subset of PWS phenotypes may arise from dysregulation of an imprinted locus distinct from the PWS region.
- Subjects :
- Male
congenital, hereditary, and neonatal diseases and abnormalities
RNA, Untranslated
Adolescent
Transcription, Genetic
Induced Pluripotent Stem Cells
Down-Regulation
Locus (genetics)
Biology
Iodide Peroxidase
Genomic Imprinting
Chromosome 15
Genetics
Humans
Epigenetics
Induced pluripotent stem cell
Gene
Oligonucleotide Array Sequence Analysis
Chromosome Aberrations
Gene Expression Profiling
Calcium-Binding Proteins
Brain
Infant
Membrane Proteins
nutritional and metabolic diseases
DNA Methylation
Fibroblasts
Chromatin
nervous system diseases
Phenotype
DNA methylation
Intercellular Signaling Peptides and Proteins
Transcriptome
Genomic imprinting
Prader-Willi Syndrome
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....d9b75a00fe6d665822a4a530bfac7820
- Full Text :
- https://doi.org/10.1038/ng.2968