Epigenetic priming of inflammatory response genes by high glucose in adipose progenitor cells

• Published in: Biochemical and biophysical research communications 2015-11, Vol.467 (4), p.979-986
• Main Authors: Rønningen, Torunn, Shah, Akshay, Reiner, Andrew H., Collas, Philippe, Moskaug, Jan Øivind
• Format: Article
• Language: English
• Subjects: Adipose stem cell; Adipose Tissue - cytology; Adipose Tissue - metabolism; Cell Differentiation; Chromatin; Chromatin - metabolism; Epigenesis, Genetic; Gene expression; Glucose; Glucose - metabolism; Histone modification; Humans; Inflammation; Inflammation - genetics; Stem Cells - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.10.030

Cellular metabolism confers wide-spread epigenetic modifications required for regulation of transcriptional networks that determine cellular states. Mesenchymal stromal cells are responsive to metabolic cues including circulating glucose levels and modulate inflammatory responses. We show here that long term exposure of undifferentiated human adipose tissue stromal cells (ASCs) to high glucose upregulates a subset of inflammation response (IR) genes and alters their promoter histone methylation patterns in a manner consistent with transcriptional de-repression. Modeling of chromatin states from combinations of histone modifications in nearly 500 IR genes unveil three overarching chromatin configurations reflecting repressive, active, and potentially active states in promoter and enhancer elements. Accordingly, we show that adipogenic differentiation in high glucose predominantly upregulates IR genes. Our results indicate that elevated extracellular glucose levels sensitize in ASCs an IR gene expression program which is exacerbated during adipocyte differentiation. We propose that high glucose exposure conveys an epigenetic ‘priming’ of IR genes, favoring a transcriptional inflammatory response upon adipogenic stimulation. Chromatin alterations at IR genes by high glucose exposure may play a role in the etiology of metabolic diseases. •Three overarching chromatin states identified at 497 IR genes in ASCs.•One of these states reflects potential for transcriptional activation.•Exposure to high glucose alters histone methylation at IR genes in ASCs.•High extracellular glucose sensitizes an IR gene expression program in ASCs.•IR gene expression is exacerbated by adipogenic stimulation in high glucose.