期刊
PHYSIOLOGICAL GENOMICS
卷 45, 期 7, 页码 287-299出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/physiolgenomics.00001.2013
关键词
high glucose; monocytes; diabetic complications; interferon regulatory factors; chromatin state
资金
- National Institutes of Health [R01 DK-065073, R01 DK-081705, R01 HL-087864]
- Juvenile Diabetes Research Foundation
Miao F, Chen Z, Zhang L, Wang J, Gao H, Wu X, Natarajan R. RNA-sequencing analysis of high glucose-treated monocytes reveals novel transcriptome signatures and associated epigenetic profiles. Physiol Genomics 45: 287-299, 2013. First published February 5, 2013; doi:10.1152/physiolgenomics.00001.2013.-We performed high throughput transcriptomic profiling with RNA sequencing (RNA-Seq) to uncover network responses in human THP-1 monocytes treated with high glucose (HG). Our data analyses revealed that interferon (IFN) signaling, pattern recognition receptors, and activated interferon regulatory factors (IRFs) were enriched among the HG-upregulated genes. Motif analysis identified an HG-responsive IRF-mediated network in which interferon-stimulated genes (ISGs) were enriched. Notably, this network showed strong overlap with a recently discovered IRF7-driven network relevant to Type 1 diabetes. We next examined if the HG-regulated genes possessed any characteristic chromatin features in the basal state by profiling 15 active and repressive chromatin marks under normal glucose conditions using chromatin immunoprecipitation linked to promoter microarrays. Composite profiles revealed higher histone H3 lysine-9-acetylation levels around the promoters of HG-upregulated genes compared with all RefSeq promoters. Interestingly, within the HG-upregulated genes, active chromatin marks were enriched not only at high CpG content promoters, but surprisingly also at low CpG content promoters. Similar results were obtained with peripheral blood monocytes exposed to HG. These new results reveal a novel mechanism by which HG can exercise IFN-alpha-like effects in monocytes by upregulating a set of ISGs poised for activation with multiple chromatin marks.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据