Donor Preference Meets Heterochromatin: Moonlighting Activities of a Recombinational Enhancer in <i>Saccharomyces cerevisiae</i>

Dodson, Anne E.; Rine, Jasper

doi:10.1534/genetics.116.194696

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…Given that RDT1 is located only 16 kb from HML , it is possible that the cohibin recruited to RDT1 by Fob1 could potentially contribute similarly to the known localization of HML near the nuclear periphery [ 65 ]. There is also evidence for the RE (left half) modifying the stability of gene silencing at HML [ 66 ], suggesting cross-talk between the two loci.…”

Section: Discussionmentioning

confidence: 99%

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III

et al. 2023

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Despite recent advances in single-molecule and structural analysis of condensin activity in vitro, mechanisms of functional condensin loading and loop extrusion that lead to specific chromosomal organization remain unclear. In Saccharomyces cerevisiae, the most prominent condensin loading site is the rDNA locus on chromosome XII, but its repetitiveness deters rigorous analysis of individual genes. An equally prominent non-rDNA condensin site is located on chromosome III (chrIII). It lies in the promoter of a putative non-coding RNA gene called RDT1, which is in a segment of the recombination enhancer (RE) that dictates MATa-specific chrIII organization. Here, we unexpectedly find that condensin is recruited to the RDT1 promoter in MATa cells through hierarchical interactions with Fob1, Tof2, and cohibin (Lrs4/Csm1), a set of nucleolar factors that also recruit condensin to the rDNA. Fob1 directly binds to this locus in vitro, while its binding in vivo depends on an adjacent Mcm1/α2 binding site that provides MATa cell specificity. We also uncover evidence for condensin-driven loop extrusion anchored by Fob1 and cohibin at RDT1 that unidirectionally extends toward MATa on the right arm of chrIII, supporting donor preference during mating-type switching. S. cerevisiae chrIII therefore provides a new platform for the study of programmed condensin-mediated chromosome conformation.

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Section: Discussionmentioning

confidence: 99%

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III

et al. 2023

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“…Interestingly, there also appears to be a function relationship between the RE and silencing at the HML locus, such that deleting the left half of the RE specifically stabilizes HML silencing in MAT a cells [36]. The mechanism involved remains unknown, but we hypothesize that eliminating this part of the RE could potentially allow the SIR and condensin complexes bound at the RDT1 promoter encroach and somehow enhance the heterochromatic structure at HML .…”

Section: Discussionmentioning

confidence: 99%

A Sir2-regulated locus control region in the recombination enhancer ofSaccharomyces cerevisiaespecifies chromosome III structure

Fine

Dinda

et al. 2019

Preprint

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22The NAD + -dependent histone deacetylase Sir2 was originally identified in Saccharomyces 23 cerevisiae as a silencing factor for HML and HMR, the heterochromatic cassettes utilized as 24 donor templates during mating-type switching. MATa cells preferentially switch to MATa using 25 HML as the donor, which is driven by an adjacent cis-acting element called the recombination 26 enhancer (RE). In this study we demonstrate that Sir2 and the condensin complex are recruited to 27 the RE exclusively in MATa cells, specifically to the promoter of a small gene within the right 28 half of the RE known as RDT1. We go on to demonstrate that the RDT1 promoter functions as a 29 locus control region (LCR) that regulates both transcription and long-range chromatin 30interactions. Sir2 represses the transcription of RDT1 until it is redistributed to a dsDNA break at 31 the MAT locus induced by the HO endonuclease during mating-type switching. Condensin is 32 also recruited to the RDT1 promoter and is displaced upon HO induction, but does not 33 significantly repress RDT1 transcription. Instead condensin appears to promote mating-type 34 switching efficiency and donor preference by maintaining proper chromosome III architecture, 35 which is defined by the interaction of HML with the right arm of chromosome III, including 36MATa and HMR. Remarkably, eliminating Sir2 and condensin recruitment to the RDT1 promoter 37 disrupts this structure and reveals an aberrant interaction between MATa and HMR, consistent 38 with the partially defective donor preference for this mutant. Global condensin subunit depletion 39 also impairs mating type switching efficiency and donor preference, suggesting that modulation 40 of chromosome architecture plays a significant role in controlling mating type switching, thus 41 providing a novel model for dissecting condensin function in vivo. 42 43 3 Author summary 44 Sir2 is a highly conserved NAD + -dependent protein deacetylase and defining member of the 45 sirtuin protein family. It was identified about 40 years ago in the budding yeast, Saccharomyces 46 cerevisiae, as a gene required for silencing of the cryptic mating-type loci, HML and HMR. 47These heterochromatic cassettes are utilized as templates for mating-type switching, whereby a 48 programmed DNA double-strand break at the MATa or MATa locus is repaired by gene 49 conversion to the opposite mating type. The preference for switching to the opposite mating type 50 is called donor preference, and in MATa cells, is driven by a cis-acting DNA element called the 51 recombination enhancer (RE). It was believed that the only role for Sir2 in mating-type 52 switching was silencing HML and HMR. However, in this study we show that Sir2 also regulates 53 expression of a small gene (RDT1) in the RE that is activated during mating-type switching. The 54 promoter of this gene is also bound by the condensin complex, and deleting this region of the RE 55 drastically changes chromosome III structure and alters donor preference. The RE therefore 56 appears ...

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“…Accordingly, a large body of literature describes engineering approaches to develop natural or synthetic promoters, terminators and transcription factor binding sites with enhanced capabilities (Redden, Morse and Alper 2014). Beyond these canonical regulations at the transcriptional level, nature has granted yeast with additional control layers that are able to elicit delicate regulation in key cellular processes, e.g., mating-type switching or adaptation to starvation (Dodson and Rine 2016;Parenteau et al 2019). Consequently, a revision of such regulatory elements, brief descriptions of the major mechanisms at play and exemplary cases of successful fine-tuning might stimulate novel engineering approaches.…”

Section: Research Article Plasmidsmentioning

confidence: 99%

Synthetic biology approaches for the construction of improved microbial cell factories

Lopez-Garcia

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Donor Preference Meets Heterochromatin: Moonlighting Activities of a Recombinational Enhancer in Saccharomyces cerevisiae

Cited by 4 publications

References 57 publications

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III

Fob1-dependent condensin recruitment and loop extrusion on yeast chromosome III

A Sir2-regulated locus control region in the recombination enhancer ofSaccharomyces cerevisiaespecifies chromosome III structure

Synthetic biology approaches for the construction of improved microbial cell factories

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