Chromatin accessibility analysis identifies the transcription factor ETV5 as a suppressor of adipose tissue macrophage activation in obesity
| Autor: | Jin-Fen Ma, Ting-Ting Yin, Kun Qu, Cai-Yue Gao, Min Ma, Zhi-Bin Zhao, Zu-Qi Zuo, Zi-Jun Li, Ren-Dong Hu, Zhe-Xiong Lian, Liang Li, Shu-Han Yang, Wen Zhang, Gui-Bin Qiao |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Adipose tissue macrophages Immunology Adipose tissue Inflammation Biology Diet High-Fat Transfection Monocytes Article Cellular and Molecular Neuroscience Mice Downregulation and upregulation medicine Macrophage Animals Humans Obesity Transcription factor QH573-671 Monocyte Macrophages Cell Biology Chronic inflammation Macrophage Activation Chromatin Cell biology DNA-Binding Proteins Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure HEK293 Cells RAW 264.7 Cells Adipose Tissue medicine.symptom Insulin Resistance Cytology Transcription Factors |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021) |
| ISSN: | 2041-4889 |
| Popis: | Activation of adipose tissue macrophages (ATMs) contributes to chronic inflammation and insulin resistance in obesity. However, the transcriptional regulatory machinery involved in ATM activation during the development of obesity is not fully understood. Here, we profiled the chromatin accessibility of blood monocytes and ATMs from obese and lean mice using assay for transposase-accessible chromatin sequencing (ATAC-seq). We found that monocytes and ATMs from obese and lean mice exhibited distinct chromatin accessibility status. There are distinct regulatory elements that are specifically associated with monocyte or ATM activation in obesity. We also discovered several transcription factors that may regulate monocyte and ATM activation in obese mice, specifically a predicted transcription factor named ETS translocation variant 5 (ETV5). The expression of ETV5 was significantly decreased in ATMs from obese mice and its downregulation was mediated by palmitate stimulation. The decrease in ETV5 expression resulted in macrophage activation. Our results also indicate that ETV5 suppresses endoplasmic reticulum (ER) stress and Il6 expression in macrophages. Our work delineates the changes in chromatin accessibility in monocytes and ATMs during obesity, and identifies ETV5 as a critical transcription factor suppressing ATM activation, suggesting its potential use as a therapeutic target in obesity-related chronic inflammation. |
| Databáze: | OpenAIRE |
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