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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.

Nucleoporin 107, 62 and 153 mediate Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells