 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 23, 2021 |
| Title |
Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses and modulates glucocorticoids receptor activity [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| 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.
|
| |
|
| Overall design |
RNA-seq of primary bone marrow-derived macrophages (BMDMs).
|
| |
|
| Contributor(s) |
Wang L, Estepa G, Ohb TG, Magida J, Obayomi SM, Chong LW, Hargreaves D, Yu RT, Atkins AR, Downes M, Wei Z, Evans RM |
| Citation(s) |
34446564 |
| |
| Submission date |
May 26, 2021 |
| Last update date |
Nov 22, 2021 |
| Contact name |
Zong Wei |
| E-mail(s) |
[email protected]
|
| Organization name |
Mayo Clinic
|
| Lab |
WEI LAB
|
| Street address |
13400 E Shea Blvd
|
| City |
SCOTTSDALE |
| State/province |
Arizona |
| ZIP/Postal code |
85259 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (31)
|
|
| This SubSeries is part of SuperSeries: |
| GSE175585 |
Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses and modulates glucocorticoids receptor activity. |
|
| Relations |
| BioProject |
PRJNA732940 |
| SRA |
SRP321498 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE175584_RNAseq1_BMDM_counts.txt.gz |
648.2 Kb |
(ftp)(http) |
TXT |
| GSE175584_RNAseq2_BMDM_counts.txt.gz |
449.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...