Potential role of DNA methylation as a facilitator of target search processes for transcription factors through interplay with methyl-CpG-binding proteins

Background.Previous studies, including ours, have examined the regulation of microRNAs (miRNAs) by DNA methylation, but whether this regulation occurs at a genome-wide level in hepatocellular carcinoma (HCC) is unclear.Subjects/Methods.Using a two-phase study design, we conducted genome-wide screening for DNA methylation and miRNA expression to explore the potential role of methylation alterations in miRNAs regulation.Results.We found that expressions of 25 miRNAs were statistically significantly different between tumor and nontumor tissues and perfectly differentiated HCC tumor from nontumor. Six miRNAs were overexpressed, and 19 were repressed in tumors. Among 133 miRNAs with inverse correlations between methylation and expression, 8 miRNAs (6%) showed statistically significant differences in expression between tumor and nontumor tissues. Six miRNAs were validated in 56 additional paired HCC tissues, and significant inverse correlations were observed for miR-125b and miR-199a, which is consistent with the inactive chromatin pattern found in HepG2 cells.Conclusion.These data suggest that the expressions of miR-125b and miR-199a are dramatically regulated by DNA hypermethylation that plays a key role in hepatocarcinogenesis.

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Biotic Stress-Induced Priming and De-Priming of Transcriptional Memory in Arabidopsis and Apple

Epigenomes ◽

10.3390/epigenomes3010003 ◽

2019 ◽

Vol 3 (1) ◽

pp. 3 ◽

Cited By ~ 2

Author(s):

Kay Gully ◽

Jean-Marc Celton ◽

Alexandre Degrave ◽

Sandra Pelletier ◽

Marie-Noelle Brisset ◽

...

Keyword(s):

Dna Methylation ◽

Potential Role ◽

Defense Responses ◽

Pathogen Resistance ◽

Growth Conditions ◽

Treatment Level ◽

Transcriptional Memory ◽

Pre Treatment

Under natural growth conditions, plants experience various and repetitive biotic and abiotic stresses. Salicylic acid (SA) is a key phytohormone involved in the response to biotic challenges. Application of synthetic SA analogues can efficiently prime defense responses, and leads to improved pathogen resistance. Because SA analogues can result in long-term priming and memory, we identified genes for which expression was affected by the SA analogue and explored the role of DNA methylation in this memorization process. We show that treatments with an SA analogue can lead to long-term transcriptional memory of particular genes in Arabidopsis. We found that subsequent challenging of such plants with a bacterial elicitor reverted this transcriptional memory, bringing their expression back to the original pre-treatment level. We also made very similar observations in apple (Malus domestica), suggesting that this expression pattern is highly conserved in plants. Finally, we found a potential role for DNA methylation in the observed transcriptional memory behavior. We show that plants defective in DNA methylation pathways displayed a different memory behavior. Our work improves our understanding of the role of transcriptional memory in priming, and has important implication concerning the application of SA analogues in agricultural settings.

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The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung

Journal of Endocrinology ◽

10.1530/joe-11-0369 ◽

2011 ◽

Vol 212 (3) ◽

pp. 291-305 ◽

Cited By ~ 19

Author(s):

Abraham B Roos ◽

Magnus Nord

Keyword(s):

Transcription Factors ◽

Potential Role ◽

Current Knowledge ◽

Inflammatory Diseases ◽

Steroid Resistance ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Glucocorticoid Signaling ◽

Enhancer Binding Protein

Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance.

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