PICH, an ATP-dependent chromatin remodeling protein, transcriptionally co-regulates oxidative stress response.

Cells respond to oxidative stress by elevating the levels of antioxidants, signaling, and transcriptional regulation often implemented by chromatin remodeling proteins. The study presented in this paper shows that the expression of PICH, an ATP-dependent chromatin remodeler, is upregulated during oxidative stress in HeLa cells. We also show that PICH regulates the expression of Nrf2, a transcription factor regulating antioxidant response, both in the absence and presence of oxidative stress. In turn, Nrf2 regulates the expression of PICH in the presence of oxidative stress. Both PICH and Nrf2 together regulate the expression of antioxidant genes and this transcriptional regulation is dependent on the ATPase activity of PICH. In addition, H3K27ac modification also plays a role in activating transcription in the presence of oxidative stress. Co-immunoprecipitation experiments show that PICH and Nrf2 interact with H3K27ac in the presence of oxidative stress. Mechanistically, PICH recognizes ARE sequences present on its target genes and introduces a conformational change to the DNA sequences leading us to hypothesize that PICH regulates transcription by remodeling DNA. PICH ablation leads to reduced expression of Nrf2 and impaired antioxidant response leading to increased ROS content, thus, showing PICH is essential for the cell to respond to oxidative stress.

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Role of Heat Shock Transcription Factor in Saccharomyces cerevisiae Oxidative Stress Response

Eukaryotic Cell ◽

10.1128/ec.00098-07 ◽

2007 ◽

Vol 6 (8) ◽

pp. 1373-1379 ◽

Cited By ~ 42

Author(s):

Ayako Yamamoto ◽

Junko Ueda ◽

Noritaka Yamamoto ◽

Naoya Hashikawa ◽

Hiroshi Sakurai

Keyword(s):

Oxidative Stress ◽

Saccharomyces Cerevisiae ◽

Transcription Factor ◽

Stress Response ◽

Heat Shock ◽

Superoxide Anion ◽

Target Genes ◽

Oxidative Stress Response ◽

Heat Shock Transcription Factor ◽

Negative Regulator

ABSTRACT The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates the transcription of a set of genes that contain heat shock elements (HSEs) in their promoters and function in diverse cellular processes, including protein folding. Here, we show that Hsf1 activates the transcription of various target genes when cells are treated with oxidizing reagents, including the superoxide anion generators menadione and KO2 and the thiol oxidants diamide and 1-chloro-2,4-dinitrobenzene (CDNB). Similar to heat shock, the oxidizing reagents are potent inducers of both efficient HSE binding and extensive phosphorylation of Hsf1. The inducible phosphorylation of Hsf1 is regulated by the intramolecular domain-domain interactions and affects HSE structure-specific transcription. Unlike the heat shock, diamide, or CDNB response, menadione or KO2 activation of Hsf1 is inhibited by cyclic-AMP-dependent protein kinase (PKA) activity, which negatively regulates the activator functions of other transcriptional regulators implicated in the oxidative stress response. These results demonstrate that Hsf1 is a member of the oxidative stress-responsive activators and that PKA is a general negative regulator in the superoxide anion response.

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The Transcription Factor Sfp1 Regulates the Oxidative Stress Response in Candida albicans

Microorganisms ◽

10.3390/microorganisms7050131 ◽

2019 ◽

Vol 7 (5) ◽

pp. 131 ◽

Cited By ~ 5

Author(s):

Shao-Yu Lee ◽

Hsueh-Fen Chen ◽

Ying-Chieh Yeh ◽

Yao-Peng Xue ◽

Chung-Yu Lan

Keyword(s):

Oxidative Stress ◽

Transcription Factor ◽

Candida Albicans ◽

Stress Response ◽

Oxidative Stress Response ◽

Antifungal Drugs ◽

Wild Type ◽

Antioxidant Genes ◽

Type C ◽

Macrophage Killing

Candida albicans is a commensal that inhabits the skin and mucous membranes of humans. Because of the increasing immunocompromised population and the limited classes of antifungal drugs available, C. albicans has emerged as an important opportunistic pathogen with high mortality rates. During infection and therapy, C. albicans frequently encounters immune cells and antifungal drugs, many of which exert their antimicrobial activity by inducing the production of reactive oxygen species (ROS). Therefore, antioxidative capacity is important for the survival and pathogenesis of C. albicans. In this study, we characterized the roles of the zinc finger transcription factor Sfp1 in the oxidative stress response against C. albicans. A sfp1-deleted mutant was more resistant to oxidants and macrophage killing than wild-type C. albicans and processed an active oxidative stress response with the phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1 and high CAP1 expression. Moreover, the sfp1-deleted mutant exhibited high expression levels of antioxidant genes in response to oxidative stress, resulting in a higher total antioxidant capacity, glutathione content, and glutathione peroxidase and superoxide dismutase enzyme activity than the wild-type C. albicans. Finally, the sfp1-deleted mutant was resistant to macrophage killing and ROS-generating antifungal drugs. Together, our findings provide a new understanding of the complex regulatory machinery in the C. albicans oxidative stress response.

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