title: The nucleoporin Nup153 regulates embryonic 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), 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.
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, 92037 California, USA.
authors.forename: Filipe V
authors.initials: FV
authors.lastname: Jacinto
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, 92037 California, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Benner
authors.affiliation: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, 92037 California, USA.
authors.forename: Martin W
authors.initials: MW
authors.lastname: Hetzer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002874:Chromosome Mapping; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D051379:Mice; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011485:Protein Binding
chemical_list: D002843:Chromatin; D028861:Nuclear Pore Complex Proteins; C513084:Nup153 protein, mouse; D063150:Polycomb Repressive Complex 1
keywords: gene silencing; nucleoporins; polycomb silencing; stem cell pluripotency; transcription