Abstract
The organization of chromatin domains in the nucleus is an important factor in gene regulation. In eukaryotic nuclei, transcriptionally silenced chromatin clusters at the nuclear periphery while transcriptionally poised chromatin resides in the nuclear interior. Recent studies suggest that nuclear pore proteins (NUPs) recruit loci to nuclear pores to aid in insulation of genes from silencing and during gene activation. We investigated the role of NUPs at a native yeast insulator and show that while NUPs localize to the native tDNA insulator adjacent to the silenced HMR domain, loss of pore proteins does not compromise insulation. Surprisingly we find that NUPs contribute to silencing at HMR and are able to restore silencing to a silencing-defective HMR allele when tethered to the locus. We show that the perinuclear positioning of heterochromatin is important for the NUP-mediated silencing effect and find that loss of NUPs result in decreased localization of HMR to the nuclear periphery. We also show that loss of telomeric tethering pathways does not eliminate NUP localization to HMR, suggesting that NUPs may mediate an independent pathway for HMR association with the nuclear periphery. We propose that localization of NUPs to the tDNA insulator at HMR helps maintain the intranuclear position of the silent locus, which in turn contributes to the fidelity of silencing at HMR.
Highlights
The regulation of gene expression is governed by the interactions between positive and negative transcription factors and DNA sequence elements
In order to determine if the nuclear pore proteins (NUPs) function as barrier proteins at this native yeast insulator, we initially inquired whether these proteins localize at or near the insulator
Nup2 is a mobile nucleoporin, whose localization to the nuclear pore complexes (NPCs) basket is dependent on Nup60 [34]
Summary
The regulation of gene expression is governed by the interactions between positive and negative transcription factors and DNA sequence elements. The higher order organization of chromatin domains within the nucleus contributes to the regulation of gene activity [1]. Active genes adopt a more open chromatin conformation while silenced genes are present within highly inaccessible chromatin domains. These open and closed chromatin domains are not randomly distributed throughout the nucleus but localize to specific regions. Silencers autonomously initiate silencing by the recruitment of sequence specific factors, which in turn recruit repressor proteins, including the Sir proteins, which deacetylate and bind histones forming a repressed chromatin domain
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