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A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure.
PLoS Genet. 2019 08; 15(8):e1008339.PG

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 MATα 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.

Authors+Show Affiliations

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.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31461456

Citation

Li, Mingguang, et al. "A Sir2-regulated Locus Control Region in the Recombination Enhancer of Saccharomyces Cerevisiae Specifies Chromosome III Structure." PLoS Genetics, vol. 15, no. 8, 2019, pp. e1008339.
Li M, Fine RD, Dinda M, et al. A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure. PLoS Genet. 2019;15(8):e1008339.
Li, M., Fine, R. D., Dinda, M., Bekiranov, S., & Smith, J. S. (2019). A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure. PLoS Genetics, 15(8), e1008339. https://doi.org/10.1371/journal.pgen.1008339
Li M, et al. A Sir2-regulated Locus Control Region in the Recombination Enhancer of Saccharomyces Cerevisiae Specifies Chromosome III Structure. PLoS Genet. 2019;15(8):e1008339. PubMed PMID: 31461456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Sir2-regulated locus control region in the recombination enhancer of Saccharomyces cerevisiae specifies chromosome III structure. AU - Li,Mingguang, AU - Fine,Ryan D, AU - Dinda,Manikarna, AU - Bekiranov,Stefan, AU - Smith,Jeffrey S, Y1 - 2019/08/28/ PY - 2019/01/25/received PY - 2019/08/01/accepted PY - 2019/09/10/revised PY - 2019/8/29/pubmed PY - 2020/1/8/medline PY - 2019/8/29/entrez SP - e1008339 EP - e1008339 JF - PLoS genetics JO - PLoS Genet VL - 15 IS - 8 N2 - 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 MATα 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/31461456/A_Sir2_regulated_locus_control_region_in_the_recombination_enhancer_of_Saccharomyces_cerevisiae_specifies_chromosome_III_structure_ DB - PRIME DP - Unbound Medicine ER -