Dynamic Trans Interactions in Yeast Chromosomes

Mirkin, Ekaterina V.; Chang, Frederick; Kleckner, Nancy

doi:10.1371/journal.pone.0075895

Cited by 11 publications

(13 citation statements)

References 75 publications

(115 reference statements)

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“…3A and Methods). We also carried out the same measurement by using two cis segments 13 kb apart on ChrXV as a positive control (22).…”

Section: Resultsmentioning

confidence: 99%

“…According to a statistical analysis of the Hi-C data, the Gal4 binding sites (GAL1 activator) cluster in the nucleus (21). β-estradiol-induced GAL1pr on two different chromosomes could form trans interactions under the activating condition in haploid yeast (22). The upstream activation sequence (UAS) of GAL1pr was able to activate transcription in trans when introduced into the Drosophila genome (23).…”

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confidence: 99%

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Interallelic interaction and gene regulation in budding yeast

Zhang

Bai

2016

Proc. Natl. Acad. Sci. U.S.A.

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In Drosophila, homologous chromosome pairing leads to "transvection," in which the enhancer of a gene can regulate the allelic transcription in trans. Interallelic interactions were also observed in vegetative diploid budding yeast, but their functional significance is unknown. Here, we show that a GAL1 reporter can interact with its homologous allele and affect its expression. By ectopically inserting two allelic reporters, one driven by wild-type GAL1 promoter (WT GAL1pr) and the other by a mutant promoter with delayed response to galactose induction, we found that the two reporters physically associate, and the WT GAL1pr triggers synchronized firing of the defective promoter and accelerates its activation without affecting its steady-state expression level. This interaction and the transregulatory effect disappear when the same reporters are located at nonallelic sites. We further demonstrated that the activator Gal4 is essential for the interallelic interaction, and the transregulation requires fully activated WT GAL1pr transcription. The mechanism of this phenomenon was further discussed. Taken together, our data revealed the existence of interallelic gene regulation in yeast, which serves as a starting point for understanding long-distance gene regulation in this genetically tractable system. homologous pairing | interallelic interaction | interallelic regulation | transvection | single-cell gene expression

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“…3A and Methods). We also carried out the same measurement by using two cis segments 13 kb apart on ChrXV as a positive control (22).…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Interallelic interaction and gene regulation in budding yeast

Zhang

Bai

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The studies so far all use the classic activation system, GAL1 promoter, as the model. It was first found that β-estradiol-induced GAL1 promoters at allelic locations could form significantly stronger transinteractions under the activating condition (Mirkin et al 2013), suggesting that this interaction is intricately related to gene expression. Extending from this observation, Zhang et al showed that two allelic reporters, one driven by wild-type GAL1 promoter and the other by a mutated GAL1 promoter with delayed response to galactose induction, physically associate upon induction.…”

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confidence: 99%

“…First, co-regulated genes can interact with each other, but only when they are located in certain genomic loci. For example, among the insertion sites tested, GAL1 reporters only interact when they are at allelic locations, or on non-homologous chromosomes but have equal distance to centromere (Mirkin et al 2013; Zhang and Bai 2016). Similarly, only a small fraction of Met4-targeted genes seems to cluster, and the MET3 reporter makes contacts with the cluster only when inserted into certain loci (Du et al 2017).…”

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confidence: 99%

3D clustering of co-regulated genes and its effect on gene expression

Bai

2017

Curr Genet

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There are extensive long-distance chromosomal interactions in eukaryotic genomes, but to what extent these interactions affect gene expression is not clear. Recent works have identified several cases where clustering of co-regulated genes leads to enhanced gene expression in budding yeast. Similar phenomenon was also observed in mammalian cells. These results challenge widely held views of gene regulation in yeast and further our understanding of how the 3D organization of the genome contribute to gene regulation in eukaryotes.

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“…3C assay was done exactly as in 39 . For each 3C template, the intensity of signal PCR product was normalized to the intensity of normalization PCR product and averaged among the triplicates.…”

Section: Methodsmentioning

confidence: 99%

Protein-Mediated Chromosome Pairing of Repetitive Arrays

Mirkin

Chang

Kleckner

2014

Journal of Molecular Biology

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Chromosomally-integrated arrays of lacO and tetO operator sites visualized by LacI and TetR repressor proteins fused with GFP (or other fluorescent proteins) are widely used to monitor the behavior of chromosomal loci in various systems. Yet, insertion of such arrays and expression of the corresponding proteins is known to perturb genomic architecture. In several cases, juxtaposition of such arrays located on different chromosomes has been inferred to reflect pairing of the corresponding loci. Here, we report that a version of TetR-GFP mutated to disrupt GFP dimerization (TetR-A206KGFP or “TetR-kGFP”), abolishes pairing of tetO-arrays in vivo and brings spatial proximity of chromosomal loci marked with those arrays back to the wild type level. These data argue that pairing of arrays is caused by GFP dimerization and thus presents an example of protein-assisted interaction in chromosomes. Arrays marked with another protein, TetR-tdTomato, which has a propensity to form intra-molecular dimers instead of inter-molecular dimers, also display reduced level of pairing, supporting this idea. TetR-kGFP provides an improved system for studying chromosomal loci with a low pairing background.

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Dynamic Trans Interactions in Yeast Chromosomes

Cited by 11 publications

References 75 publications

Interallelic interaction and gene regulation in budding yeast

Interallelic interaction and gene regulation in budding yeast

3D clustering of co-regulated genes and its effect on gene expression

Protein-Mediated Chromosome Pairing of Repetitive Arrays

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