The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing

Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the acti...

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Bibliographic Details
Published in:Genes & development 2015-06, Vol.29 (12), p.1224-1238
Main Authors: Jacinto, Filipe V, Benner, Chris, Hetzer, Martin W
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell Differentiation
Cell Nucleus - metabolism
Chromatin - metabolism
Chromosome Mapping
Embryonic Stem Cells - cytology
Embryonic Stem Cells - physiology
Epigenesis, Genetic
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Gene Silencing
Mice
Nuclear Pore Complex Proteins - genetics
Nuclear Pore Complex Proteins - metabolism
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - physiology
Polycomb Repressive Complex 1 - metabolism
Protein Binding
Research Paper
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Summary:Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.260919.115