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Nuclear pore complexes mediate subtelomeric gene silencing by regulating PCNA levels on chro atin

ABSTRACT: The nuclear pore complex (NPC) physically interacts with chromatin and regulates gene expression. The Saccharomyces cerevisiae inner ring nucleoporin Nup170 has been implicated in chromatin organization and the maintenance of gene silencing in subtelomeric regions. To gain insight into how Nup170 regulates this process, we used protein-protein interactions, genetic interactions, and transcriptome correlation analyses to identify the Ctf18-RFC complex, an alternative proliferating cell nuclear antigen (PCNA) loader, as a facilitator of the gene regulatory functions of Nup170. The Ctf18-RFC complex is recruited to a subpopulation of NPCs that lack the nuclear basket proteins Mlp1 and Mlp2. In the absence of Nup170, PCNA levels on DNA are reduced, resulting in the loss of silencing of subtelomeric genes. Increasing PCNA levels on DNA by removing Elg1, which is required for PCNA unloading, rescues subtelomeric silencing defects in nup170Δ. The NPC therefore mediates subtelomeric gene silencing by regulating PCNA levels on DNA.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Arti Navare

LAB HEAD: John D. Aithicson

PROVIDER: PXD041496 | Pride | 2023-06-13

REPOSITORIES: Pride

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	AN062118_062818_A1.raw	Raw
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	AN062118_062818_A11.raw	Raw
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	AN062118_062818_A3.raw	Raw

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A role for the nucleoporin Nup170p in chromatin structure and gene silencing

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A role for the nucleoporin Nup170p in chromatin structure and gene silencing [Agilent ChIP-chip]

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2013-02-28 | E-GEOD-36794 | biostudies-arrayexpress

A role for the nucleoporin Nup170p in chromatin structure and gene silencing [Agilent microarrays]

Project description:Embedded in the nuclear envelope, nuclear pore complexes (NPCs) not only regulate nuclear transport, but also interface with both transcriptionally active euchromatin and largely silenced heterochromatin, as well as the boundaries between these regions. It is unclear what functional role NPCs play in establishing or maintaining these distinct chromatin domains. Here we report that the yeast NPC protein Nup170p interacts with specific regions of the genome containing ribosomal protein and subtelomeric genes. At these locations, Nup170p functions to establish normal nucleosome positioning and as a repressor of transcription. We show that the function of Nup170p in subtelomeric gene silencing is linked to its association with the RSC chromatin-remodeling complex and the silencing factor Sir4p, and that the binding of Nup170p and Sir4p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope. Our results establish the NPC as an active participant in the formation of peripheral heterochromatin. Two-color microarrays were performed using Agilent whole-genome Saccharomyces cerevisiae arrays (Agilent) to determine gene expression profiles in the nucleoporin mutant strains nup157M-bM-^HM-^F, nup170M-bM-^HM-^F, and nup188M-bM-^HM-^F. Similar analyses were performed on PMET3-HA3-STH1 cells depleted of Sth1p for either 2 hrs (sth1-deplete 2hrs) or depleted of Sth1p for 8 hrs followed by reinduction of Sth1p for an additional 4 hrs (sth1-reinduction 4hr), as well as WT cells grown in the presence or absence of methionine. All experiments were performed with duplicate experimental and duplicate technical replicates of each condition as previously described (Wan et al., 2009).

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The nucleoporin Nup170p is required for subtelomeric chromatin structure and gene silencing. [MNase-Seq]

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Sir4 H-BRCT domain interacts with multiple phospho-proteins to regulate heterochromatic repression

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Chromatin Assembly Factor 1 (CAF-1) facilitates the establishment of facultative heterochromatin during pluripotency exit

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