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Chromatin accessibility analysis identifies the transcription factor ETV5 as a suppressor of adipose tissue macrophage activation in obesity
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 11, Pp 1-11 (2021)
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell deathdisease
- Accession number :
- edsair.doi.dedup.....ea7a85894cac4023be06c0636d269b73