Transcriptional Regulation of 15-Lipoxygenase Expression by Histone H3 Lysine 4 Methylation/Demethylation
| العنوان: | Transcriptional Regulation of 15-Lipoxygenase Expression by Histone H3 Lysine 4 Methylation/Demethylation |
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| المؤلفون: | Frida Schain, Dawei Xu, Hans-Erik Claesson, Hongya Han, Cheng Liu, Yidong Fan, Zhonghua Xu, Magnus Björkholm, Jan Sjöberg |
| المصدر: | PLoS ONE PLoS ONE, Vol 7, Iss 12, p e52703 (2012) |
| بيانات النشر: | Public Library of Science, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Transcriptional Activation, Histone H3 Lysine 4, Transcription, Genetic, DNA transcription, lcsh:Medicine, Gene Expression, Biology, Biochemistry, Methylation, Models, Biological, Cell Line, Molecular Genetics, Histones, Molecular cell biology, Histone methylation, Histone H2A, Genetics, Arachidonate 15-Lipoxygenase, Humans, Gene Regulation, Histone H3 acetylation, lcsh:Science, Promoter Regions, Genetic, Epigenomics, Regulation of gene expression, Histone Demethylases, Multidisciplinary, integumentary system, Lysine, EZH2, lcsh:R, Fatty Acids, Computational Biology, Oxidoreductases, N-Demethylating, Histone-Lysine N-Methyltransferase, Lipid Metabolism, Chromatin Assembly and Disassembly, Molecular biology, Lipids, Chromatin, Gene Expression Regulation, Histone methyltransferase, lcsh:Q, lipids (amino acids, peptides, and proteins), Histone modification, STAT6 Transcription Factor, Research Article, Protein Binding |
| الوصف: | 15-Lipoxygenase-1 (15-LOX-1) oxidizes polyunsaturated fatty acids to a rich spectrum of biologically active metabolites and is implicated in physiological membrane remodelling, inflammation and apoptosis. Its deregulation is involved in the pathogenesis of diverse cancer and immune diseases. Recent experimental evidence reveals that dynamic histone methylation/demethylation mediated by histone methyltransferases and demethylases plays a critical role in regulation of chromatin remodelling and gene expression. In the present study, we compared the histone 3 lysine 4 (H3-K4) methylation status of the 15-LOX-1 promoter region of the two Hodgkin lymphoma (HL) cell lines L1236 and L428 with abundant and undetectable 15-LOX-1 expression, respectively. We identified a potential role of H3-K4 methylation in positive regulation of 15-LOX-1 transcription. Furthermore, we found that histone methyltransferase SMYD3 inhibition reduced 15-LOX-1 expression by decreasing promoter activity in L1236 cells. SMYD3 knock down in these cells abolished di−/trimethylation of H3-K4, attenuated the occupancy by the transactivator STAT6, and led to diminished histone H3 acetylation at the 15-LOX-1 promoter. In contrast, inhibition of SMCX, a JmjC-domain-containing H3-K4 tri-demethylase, upregulated 15-LOX-1 expression through induction of H3-K4 trimethylation, histone acetylation and STAT6 recruitment at the 15-LOX-1 promoter in L428 cells. In addition, we observed strong SMYD3 expression in the prostate cancer cell line LNCaP and its inhibition led to decreased 15-LOX-1 expression. Taken together, our data suggest that regulation of histone methylation/demethylation at the 15-LOX-1 promoter is important in 15-LOX-1 expression. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::493fc209ad6beab262ac4a6b145258ebTest http://europepmc.org/articles/PMC3532411Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....493fc209ad6beab262ac4a6b145258eb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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