Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-05208-2
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Funding
- Canadian Institutes of Health Research [MOP 111210]
- Western University
- Schulich School of Medicine
- Lawson Health Research Institute
- Magee-Womens Research Institute
- University of Pittsburgh
- Western University Obstetrics and Gynaecology Student Fellowship
- Children's Health Research Institute Curtis Cadman Studentship
- Lawson Health Research Institute Graduate Fellowship
- Magee-Women's Research Institute Paul M. Rike Postdoctoral Fellowship
- NSERC Canada Graduate Scholarship
- Ontario Graduate Scholarship
- Children's Health Research Institute Postdoctoral Fellowship
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Genomic imprinting is a phenomenon that restricts transcription to predominantly one parental allele. How this transcriptional duality is regulated is poorly understood. Here we perform an RNA interference screen for epigenetic factors involved in paternal allelic silencing at the Kcnq1ot1 imprinted domain in mouse extraembryonic endoderm stem cells. Multiple factors are identified, including nucleoporin 107 (NUP107). To determine NUP107's role and specificity in Kcnq1ot1 imprinted domain regulation, we deplete Nup107, as well as Nup62, Nup98/96 and Nup153. Nup107, Nup62 and Nup153, but not Nup98/96 depletion, reduce Kcnq1ot1 noncoding RNA volume, displace the Kcnq1ot1 domain from the nuclear periphery, reactivate a subset of normally silent paternal alleles in the domain, alter histone modifications with concomitant changes in KMT2A, EZH2 and EHMT2 occupancy, as well as reduce cohesin interactions at the Kcnq1ot1 imprinting control region. Our results establish an important role for specific nucleoporins in mediating Kcnq1ot1 imprinted domain regulation.
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