Synergy of Hir1, Ssn6, and Snf2 global regulators is the functional determinant of a Mac1 transcriptional switch in S. cerevisiae copper homeostasis
| Autor: | George S Fragiadakis, Alexandra Voutsina, Kalliopi Gkouskou, Despina Alexandraki |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Saccharomyces cerevisiae Repressor RNA polymerase II Chromatin remodeling 03 medical and health sciences Gene Expression Regulation Fungal Genetics Homeostasis Nucleosome Promoter Regions Genetic Cation Transport Proteins Gene Copper Transporter 1 030304 developmental biology Adenosine Triphosphatases 0303 health sciences biology 030302 biochemistry & molecular biology Nuclear Proteins General Medicine biology.organism_classification Cell biology Repressor Proteins Histone Chaperone (protein) biology.protein Copper Transcription Factors |
| Zdroj: | Current Genetics. 65:799-816 |
| ISSN: | 1432-0983 0172-8083 |
| DOI: | 10.1007/s00294-019-00935-5 |
| Popis: | To gain insights on the transcriptional switches that modulate proper copper homeostasis in yeast, we have examined in detail functional interactions of the relevant transcriptional activator Mac1. We identified Hir1 transcriptional repressor and histone chaperone as a Mac1-interacting protein. This association directly recruits Hir1 on a Mac1 target, CTR1 promoter, quantitatively under induction conditions. We also found Hir1 interacting directly with a previously unknown partner, the Ssn6 (Cyc8) co-regulator. On the non-induced CTR1 promoter, a Hir1 transcriptional activation function was revealed, in the absence of Ssn6, which was dependent on the presence of Snf2 (Swi2) nucleosome remodeler. Moreover, Ssn6 was identified as a Mac1-dependent prominent repressor of CTR1 transcription, antagonizing Snf2 occupancy. Transcriptional induction by copper depletion was effected by the quantitative recruitment of Snf2 directed mainly by Mac1 and redundantly by the quantitatively accumulated Hir1 and Ssn6 pair. Our analysis showed that the activation-effecting chromatin remodeling of CTR1 was due to Snf2 and not to the Hir1 histone chaperone activity or ability to regulate histone levels and stoichiometry. Following initiation, Hir1 and Snf2, but not Ssn6, were found to associate also with the actively transcribing CTR1 coding region, where Hir1 followed the pattern of the elongating RNA polymerase II. Therefore, we have shown that, at the CTR1 gene, in association with Mac1 DNA-binding transcriptional activator, the distinct and alternate genetic and physical collaboration of three global regulators modulates the transcriptional state of a switch involved in copper homeostasis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink