Low activity of LSD1 elicits a pro-inflammatory gene expression profile in riboflavin-deficient human T lymphoma Jurkat cells

Dandan Liu, Janos Zempleni

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14 Citations (Scopus)

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 proinflammatory 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.

Original languageEnglish (US)
Article number422
JournalGenes and Nutrition
Volume9
Issue number5
DOIs
StatePublished - Sep 2014

Fingerprint

Jurkat Cells
Riboflavin
Transcriptome
Lysine
Lymphoma
Flavin-Adenine Dinucleotide
Riboflavin Deficiency
Cytokines
Interleukin-1
Transcriptional Activation
Genes
Lysergic Acid Diethylamide
Messenger RNA
Transcription Initiation Site
Epigenomics
Histones
Culture Media
Exons
Interleukin-6
Cell Culture Techniques

Keywords

  • Demethylation
  • FAD
  • H3K4me2
  • LSD1
  • Pro-inflammatory cytokines
  • TSS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics

Cite this

@article{238c62def2a0459c96020bbe1441c663,
title = "Low activity of LSD1 elicits a pro-inflammatory gene expression profile in riboflavin-deficient human T lymphoma Jurkat cells",
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 proinflammatory 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.",
keywords = "Demethylation, FAD, H3K4me2, LSD1, Pro-inflammatory cytokines, TSS",
author = "Dandan Liu and Janos Zempleni",
year = "2014",
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doi = "10.1007/s12263-014-0422-6",
language = "English (US)",
volume = "9",
journal = "Genes and Nutrition",
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TY - JOUR

T1 - Low activity of LSD1 elicits a pro-inflammatory gene expression profile in riboflavin-deficient human T lymphoma Jurkat cells

AU - Liu, Dandan

AU - Zempleni, Janos

PY - 2014/9

Y1 - 2014/9

N2 - 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 proinflammatory 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.

AB - 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 proinflammatory 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.

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KW - Pro-inflammatory cytokines

KW - TSS

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