| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Liu, Dandan Zempleni, Janos |
| Abstract | Mono- and dimethylation of lysine (K)-4 in histone H3 (H3K4me1, H3K4me2) create epigenetic gene activation marks that are enriched near the transcription start site of genes. Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD)-dependent demethylase that catalyzes the demethylation of H3K4me1 and H3K4me2, thereby mediating gene repression. This study tested the hypothesis that LSD1 activity depends on the concentrations of the FAD precursor, riboflavin, in cell culture media, and that riboflavin deficiency causes derepression of pro-inflammatory cytokines. Human T lymphoma Jurkat cells were cultured in riboflavin-defined media, representing plasma levels of riboflavin in moderately deficient, sufficient, and supplemented humans. The expression of LSD1 mRNA and protein followed the pattern riboflavin-deficient > riboflavin-sufficient > riboflavin-supplemented cells. However, the increase in LSD1 expression was insufficient to compensate for FAD depletion, and LSD activities were more than 30 % higher in riboflavin-supplemented cells compared with the other treatment groups. The enrichment of H3K4me2 marks was 11–137 % greater in riboflavin-deficient cells compared with sufficient cells in exon 1 of genes coding for the pro-inflammatory cytokines interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor-α. Consistent with the enrichment of gene activation marks, the expression of mRNA coding for pro-inflammatory cytokines was 62–487 % higher in riboflavin-deficient cells compared with sufficient cells. These findings support the hypothesis that riboflavin deficiency contributes toward a pro-inflammatory gene expression pattern through a loss of LSD1 activity. |
| Related Links | https://genesandnutrition.biomedcentral.com/counter/pdf/10.1007/s12263-014-0422-6.pdf |
| Ending Page | 8 |
| Page Count | 8 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 18653499 |
| DOI | 10.1007/s12263-014-0422-6 |
| Journal | Genes & Nutrition |
| Issue Number | 5 |
| Volume Number | 9 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2014-08-08 |
| Access Restriction | Open |
| Subject Keyword | Human Genetics Clinical Nutrition Gene Function Biomedicine LSD1 Demethylation FAD H3K4me2 Pro-inflammatory cytokines TSS |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Genetics |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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