Role of Epigenetic Modifications in Plant Responses to Environmental Stresses

Liu, Xuncheng; Luo, Ming; Yang, Shi-Nine; Wu, Keqiang

doi:10.1007/978-1-4939-2386-1_5

Cited by 6 publications

(2 citation statements)

References 74 publications

(85 reference statements)

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“…ELP2 is a subunit of the Elongator complex, a histone acetyltransferase that regulates gene expression and is well conserved across eukaryotes [ 17 ]. Previous work demonstrates that Elongator complex plays a critical role in environmental stress response, including oxidative stress [ 18 , 19 ]. TMOD1 reportedly possesses peroxisome activity and plays a role in antioxidant defense [ 20 , 21 ].…”

Section: Resultsmentioning

confidence: 99%

Understanding and Controlling Sialylation in a CHO Fc-Fusion Process

et al. 2016

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A Chinese hamster ovary (CHO) bioprocess, where the product is a sialylated Fc-fusion protein, was operated at pilot and manufacturing scale and significant variation of sialylation level was observed. In order to more tightly control glycosylation profiles, we sought to identify the cause of variability. Untargeted metabolomics and transcriptomics methods were applied to select samples from the large scale runs. Lower sialylation was correlated with elevated mannose levels, a shift in glucose metabolism, and increased oxidative stress response. Using a 5-L scale model operated with a reduced dissolved oxygen set point, we were able to reproduce the phenotypic profiles observed at manufacturing scale including lower sialylation, higher lactate and lower ammonia levels. Targeted transcriptomics and metabolomics confirmed that reduced oxygen levels resulted in increased mannose levels, a shift towards glycolysis, and increased oxidative stress response similar to the manufacturing scale. Finally, we propose a biological mechanism linking large scale operation and sialylation variation. Oxidative stress results from gas transfer limitations at large scale and the presence of oxygen dead-zones inducing upregulation of glycolysis and mannose biosynthesis, and downregulation of hexosamine biosynthesis and acetyl-CoA formation. The lower flux through the hexosamine pathway and reduced intracellular pools of acetyl-CoA led to reduced formation of N-acetylglucosamine and N-acetylneuraminic acid, both key building blocks of N-glycan structures. This study reports for the first time a link between oxidative stress and mammalian protein sialyation. In this study, process, analytical, metabolomic, and transcriptomic data at manufacturing, pilot, and laboratory scales were taken together to develop a systems level understanding of the process and identify oxygen limitation as the root cause of glycosylation variability.

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Section: Resultsmentioning

confidence: 99%

Understanding and Controlling Sialylation in a CHO Fc-Fusion Process

et al. 2016

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“…Regulation of response to salt stress is a complex process controlled by developmental and environmental signaling pathways (Ingram and Bartels, 1996;Xiong et al, 2002;Shinozaki et al, 2003;Bohnert et al, 2006;Jeandroz and Lamotte, 2017). Recent results have shown that histone acetylation/deacetylation is an essential process in the epigenetic regulation of gene expression involved in plant response to environmental changes and stress (Kawashima and Berger, 2014;Liu et al, 2015;Shen et al, 2015). The dynamic equilibrium between histone acetyltransferases and histone deacetylases (HDACs) controls histone acetylation levels of nucleosomes, affecting chromatin structure and gene activity (Mikkelsen et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Histone Deacetylase HDA9 and WRKY53 Transcription Factor Are Mutual Antagonists in Regulation of Plant Stress Response

Zheng¹,

Ge²,

Bao³

et al. 2020

Molecular Plant

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Epigenetic regulation of gene expression is important for plant adaptation to environmental changes. Previous results showed that Arabidopsis RPD3-like histone deacetylase HDA9 is known to function in repressing plant response to stress in Arabidopsis. However, how HDA9 targets to specific chromatin loci and controls gene expression networks involved in plant response to stress remains largely unclear. Here, we show that HDA9 represses stress tolerance response by interacting with and regulating the DNA binding and transcriptional activity of WRKY53, which functions as a high-hierarchy positive regulator of stress response. We found that WRKY53 is post-translationally modified by lysine acetylation at multiple sites, some of which are removed by HDA9, resulting in inhibition of WRKY53 transcription activity. Conversely, WRKY53 negatively regulates HDA9 histone deacetylase activity. Collectively, our results indicate that HDA9 and WRK53 are reciprocal negative regulators of each other's activities, illustrating how the functional interplay between a chromatin regulator and a transcription factor regulates stress tolerance in plants.

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