| Title: | A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure |
| Author(s): | Li M; Fine RD; Dinda M; Bekiranov S; Smith JS; |
| Address: | "Department of Laboratory Medicine, Jilin Medical University, Jilin, China. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America" |
| DOI: | 10.1371/journal.pgen.1008339 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "The NAD+-dependent histone deacetylase Sir2 was originally identified in Saccharomyces cerevisiae as a silencing factor for HML and HMR, the heterochromatic cassettes utilized as donor templates during mating-type switching. MATa cells preferentially switch to MATalpha using HML as the donor, which is driven by an adjacent cis-acting element called the recombination enhancer (RE). In this study we demonstrate that Sir2 and the condensin complex are recruited to the RE exclusively in MATa cells, specifically to the promoter of a small gene within the right half of the RE known as RDT1. We also provide evidence that the RDT1 promoter functions as a locus control region (LCR) that regulates both transcription and long-range chromatin interactions. Sir2 represses RDT1 transcription until it is removed from the promoter in response to a dsDNA break at the MAT locus induced by HO endonuclease during mating-type switching. Condensin is also recruited to the RDT1 promoter and is displaced upon HO induction, but does not significantly repress RDT1 transcription. Instead condensin appears to promote mating-type donor preference by maintaining proper chromosome III architecture, which is defined by the interaction of HML with the right arm of chromosome III, including MATa and HMR. Remarkably, eliminating Sir2 and condensin recruitment to the RDT1 promoter disrupts this structure and reveals an aberrant interaction between MATa and HMR, consistent with the partially defective donor preference for this mutant. Global condensin subunit depletion also impairs mating-type switching efficiency and donor preference, suggesting that modulation of chromosome architecture plays a significant role in controlling mating-type switching, thus providing a novel model for dissecting condensin function in vivo" |
| Keywords: | "Adenosine Triphosphatases/metabolism Chromosomes, Fungal/*genetics DNA-Binding Proteins/metabolism Genes, Mating Type, Fungal/*genetics Genetic Loci/genetics Locus Control Region/*genetics Multiprotein Complexes/metabolism Promoter Regions, Genetic/geneti;" |
| Notes: | "MedlineLi, Mingguang Fine, Ryan D Dinda, Manikarna Bekiranov, Stefan Smith, Jeffrey S eng R01 GM075240/GM/NIGMS NIH HHS/ R01 GM127394/GM/NIGMS NIH HHS/ R21 GM110380/GM/NIGMS NIH HHS/ T32 GM008136/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2019/08/29 PLoS Genet. 2019 Aug 28; 15(8):e1008339. doi: 10.1371/journal.pgen.1008339. eCollection 2019 Aug" |
