The head module of Mediator directs activation of preloaded RNAPII in vivo

Lee, Sarah K.; Xu, Chao; Huang, Lin; Stargell, Laurie A.

doi:10.1093/nar/gkt796

Cited by 8 publications

(8 citation statements)

References 83 publications

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“…Recent results in yeast have shown that TFIIH-dependent pol II CTD phosphorylation contributes to, but is not required for, the disruption of Mediator–pol II contacts at the promoter 83,84 . Whereas promoter-proximal paused pol II does not appear to be a common regulatory intermediate in yeast 85 , these and other 86 findings suggest a conserved role for Mediator in regulation of pol II promoter escape.…”

Section: Mediator Roles In Pol II Transcriptionmentioning

confidence: 57%

The Mediator complex: a central integrator of transcription

Allen

Taatjes

2015

Nat Rev Mol Cell Biol

742

713

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The RNA polymerase II (pol II) enzyme transcribes all protein-coding and most non-coding RNA genes and is globally regulated by Mediator, a large, conformationally flexible protein complex with variable subunit composition (for example, a four-subunit CDK8 module can reversibly associate). These biochemical characteristics are fundamentally important for Mediator's ability to control various processes important for transcription, including organization of chromatin architecture and regulation of pol II pre-initiation, initiation, re-initiation, pausing, and elongation. Although Mediator exists in all eukaryotes, a variety of Mediator functions appear to be specific to metazoans, indicative of more diverse regulatory requirements.

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Section: Mediator Roles In Pol II Transcriptionmentioning

confidence: 57%

The Mediator complex: a central integrator of transcription

Allen

Taatjes

2015

Nat Rev Mol Cell Biol

742

713

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“…In Saccharomyces cerevisiae, Mediator subunits Med18, Med19, and Med20, which activate the cytochrome c 1 (CYC1) gene in response to oxidative stress, are required for cell viability (17). Med17 links transcription and DNA repair by facilitating the recruitment of the Rad2/XPG endonuclease to transcribed genes during exogenous genotoxic stress (18).…”

mentioning

confidence: 99%

Med15B Regulates Acid Stress Response and Tolerance in Candida glabrata by Altering Membrane Lipid Composition

Liu

et al. 2017

Appl Environ Microbiol

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Candida glabrata is a promising producer of organic acids. To elucidate the physiological function of the Mediator tail subunit Med15B in the response to low-pH stress, we constructed a deletion strain, C. glabrata med15BΔ, and an overexpression strain, C. glabrata HTUΔ/CgMED15B. Deletion of MED15B caused biomass production, glucose consumption rate, and cell viability to decrease by 28.3%, 31.7%, and 26.5%, respectively, compared with those of the parent (HTUΔ) strain at pH 2.0. Expression of lipid metabolism-related genes was significantly downregulated in the med15BΔ strain, whereas key genes of ergosterol biosynthesis showed abnormal upregulation. This caused the proportion of C 18:1 fatty acids, the ratio of unsaturated to saturated fatty acids (UFA/SFA), and the total phospholipid content to decrease by 11.6%, 27.4%, and 37.6%, respectively. Cells failed to synthesize fecosterol and ergosterol, leading to the accumulation and a 60.3-fold increase in the concentration of zymosterol. Additionally, cells showed reductions of 69.2%, 11.6%, and 21.8% in membrane integrity, fluidity, and H ϩ -ATPase activity, respectively. In contrast, overexpression of Med15B increased the C 18:1 levels, total phospholipids, ergosterol content, and UFA/SFA by 18.6%, 143.5%, 94.5%, and 18.7%, respectively. Membrane integrity, fluidity, and H ϩ -ATPase activity also increased by 30.2%, 6.9%, and 51.8%, respectively. Furthermore, in the absence of pH buffering, dry weight of cells and pyruvate concentrations were 29.3% and 61.2% higher, respectively, than those of the parent strain. These results indicated that in C. glabrata, Med15B regulates tolerance toward low pH via transcriptional regulation of acid stress response genes and alteration in lipid composition. IMPORTANCE This study explored the role of the Mediator tail subunit Med15B in the metabolism of Candida glabrata under acidic conditions. Overexpression of MED15B enhanced yeast tolerance to low pH and improved biomass production, cell viability, and pyruvate yield. Membrane lipid composition data indicated that Med15B might play a critical role in membrane integrity, fluidity, and H ϩ -ATPase activity homeostasis at low pH. Thus, controlling membrane composition may serve to increase C. glabrata productivity at low pH.KEYWORDS Candida glabrata, Mediator subunit Med15B, low-pH stress, transcriptomics, membrane lipid T he Mediator coactivator complex is required for transcription initiation in eukaryotes (1, 2). It is recruited by transcription activators and conveys regulatory information from gene-specific regulators to promoters (3, 4). Mediator can influence almost all stages of transcription and coordinated processes such as chromatin remodeling, transcription elongation, and posttranslational modifications (5, 6). Mediator is a multisubunit assembly comprising four modules: head, middle, tail, and cyclin-dependent kinase 8 (CDK8) (7). The head and middle modules are highly

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“…Therefore, in low-oxygen conditions (hypoxic growth), Rox1p is not expressed, and hypoxia-related genes are upregulated (reviewed by Siso et al [ 86 ]). In our study, melatonin downregulated genes related to aerobic conditions in non-stressed cells (mitochondrial or nonmitochondrial) that are targets of Hap1p ( NDE1 , CYC1 but also CIR2 and CLD1 ), Hap2/3/4/5 complex ( COX5A , COX4 but also INH1 ) or both factors ( CYT1 , RIP1 ) ( Figure 7 , Dataset S1 ) [ 79 , 87 ].…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Insights into the Effect of Melatonin in Saccharomyces cerevisiae in the Presence and Absence of Oxidative Stress

et al. 2020

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Melatonin is a ubiquitous indolamine that plays important roles in various aspects of biological processes in mammals. In Saccharomyces cerevisiae, melatonin has been reported to exhibit antioxidant properties and to modulate the expression of some genes involved in endogenous defense systems. The aim of this study was to elucidate the role of supplemented melatonin at the transcriptional level in S. cerevisiae in the presence and absence of oxidative stress. This was achieved by exposing yeast cells pretreated with different melatonin concentrations to hydrogen peroxide and assessing the entry of melatonin into the cell and the yeast response at the transcriptional level (by microarray and qPCR analyses) and the physiological level (by analyzing changes in the lipid composition and mitochondrial activity). We found that exogenous melatonin crossed cellular membranes at nanomolar concentrations and modulated the expression of many genes, mainly downregulating the expression of mitochondrial genes in the absence of oxidative stress, triggering a hypoxia-like response, and upregulating them under stress, mainly the cytochrome complex and electron transport chain. Other categories that were enriched by the effect of melatonin were related to transport, antioxidant activity, signaling, and carbohydrate and lipid metabolism. The overall results suggest that melatonin is able to reprogram the cellular machinery to achieve tolerance to oxidative stress.

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The head module of Mediator directs activation of preloaded RNAPII in vivo

Cited by 8 publications

References 83 publications

The Mediator complex: a central integrator of transcription

The Mediator complex: a central integrator of transcription

Med15B Regulates Acid Stress Response and Tolerance in Candida glabrata by Altering Membrane Lipid Composition

Transcriptomic Insights into the Effect of Melatonin in Saccharomyces cerevisiae in the Presence and Absence of Oxidative Stress

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