期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 467, 期 4, 页码 979-986出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.10.030
关键词
Adipose stem cell; Chromatin; Gene expression; Glucose; Histone modification; Inflammation
资金
- Research Council of Norway
- Norwegian Center for Stem Cell Research
- University of Oslo
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. (C) 2015 Elsevier Inc. All rights reserved.
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