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Nucleoporin Nup153 Regulates Stem Cell Pluripotency through Gene Silencing

ABSTRACT: Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), the transport channels that mediate nuclear transport. Recent evidence suggest 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 de-repression of developmental genes and induction of early differentiation. This loss of pluripotency is not associated with defects in global nucleo-cytoplasmic transport activity. Instead, Nup153 binds to the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb repressive complex 1 (PRC1) to its target loci. Our results reveal a nuclear transport-independent role of Nup153 in maintaining stem cell pluripotency and introduce a role of NPC proteins in mammalian epigenetic gene silencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE64008 | GEO | 2015/06/19

SECONDARY ACCESSION(S): PRJNA269747

REPOSITORIES: GEO

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Nucleoporin Nup153 Regulates Stem Cell Pluripotency through Gene Silencing

Project description:Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), the transport channels that mediate nuclear transport. Recent evidence suggest 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 de-repression of developmental genes and induction of early differentiation. This loss of pluripotency is not associated with defects in global nucleo-cytoplasmic transport activity. Instead, Nup153 binds to the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb repressive complex 1 (PRC1) to its target loci. Our results reveal a nuclear transport-independent role of Nup153 in maintaining stem cell pluripotency and introduce a role of NPC proteins in mammalian epigenetic gene silencing. RNA-seq, ChIP-Seq, and DamID-Seq for Nup153, Oct4, and key chromatin regulators in mouse ES cells and neural progenitors

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Nucleoporin 153 links nuclear pore complex to chromatin architecture by mediating CTCF and cohesin binding (ChIP-Seq)

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