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University of California-San Diego: Dataset Details, ID=GSE175582

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Superfund Research Program

Detection and Models of Toxicant Exposure

Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2023
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Title: Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses and modulates glucocorticoids receptor activity [ChIP-seq]

Accession Number: GSE175582

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE175582

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Genome binding/occupancy profiling by high throughput sequencing

Organism(s): Mus musculus

Summary: In macrophages, homeostatic and immune signals induce distinct sets of transcriptional responses, defining the cellular identity and function. The activity of lineage specific and signal induced transcription factors are regulated by chromatin accessibility and other epigenetic modulators. Glucocorticoids are potent anti-inflammatory drugs. Acting through the glucocorticoid receptor (GR), glucocorticoids directly repress inflammatory responses at transcriptional and epigenetic levels in macrophages. In this study, we identified bromodomain containing 9 (BRD9), a component of SWI/SNF chromatin remodeling complex, as a novel modulator for glucocorticoids responses in macrophages. Inhibition, degradation, or genetic depletion of BRD9 in bone marrow derived macrophages (BMDM), significantly compromised their responses to inflammatory stimuli, such as liposaccharides (LPS), and interferons. A large portion of BRD9-regulated genes are also known to be regulated by dexamethasone, a synthetic glucocorticoid. Importantly, pharmacologic inhibition of BRD9 is able to further potentiate the anti-inflammatory responses of dexamethasone, by further repressing the GR downstream targets. Mechanistically, BRD9 co-localized with a subset of GR binding sites. Depletion of BRD9 enhanced GR occupancy at a subset of its targets. Enhanced occupancy of GR at these sites is associated with further repression of inflammation-related genes. Collectively, these findings establish BRD9 as a key modulator of macrophage inflammatory responses, revealing the therapeutic potential of BRD9 inhibitors as modulators for glucocorticoids action.

Publication(s) associated with this dataset:
  • Wang L, Oh TG, Magida J, Estepa G, Obayomi SB, Chong L, Gatchalian J, Yu RT, Atkins AR, Hargreaves D, Downes M, Wei Z, Evans RM. 2021. Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses by potentiating glucocorticoid receptor activity. Proc Natl Acad Sci U S A 118(35):e2109517118. doi:10.1073/pnas.2109517118 PMID:34446564 PMCID:PMC8536317
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