Title |
The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome
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Published in |
Nature Genetics, May 2014
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DOI | 10.1038/ng.2968 |
Pubmed ID | |
Authors |
Yonatan Stelzer, Ido Sagi, Ofra Yanuka, Rachel Eiges, Nissim Benvenisty |
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. |
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United Kingdom | 3 | 33% |
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Demographic breakdown
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Scientists | 3 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 11% |
Mendeley readers
Geographical breakdown
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Japan | 2 | 1% |
United Kingdom | 1 | <1% |
China | 1 | <1% |
Canada | 1 | <1% |
Mexico | 1 | <1% |
Spain | 1 | <1% |
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Student > Doctoral Student | 11 | 6% |
Other | 32 | 17% |
Unknown | 21 | 11% |
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Computer Science | 2 | 1% |
Other | 8 | 4% |
Unknown | 27 | 14% |