 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jan 30, 2015 |
| Title |
A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages. |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8–PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF–AP-1 sites, which were not premarked by PU.1 and did not contribute to the basal IRF8 cistrome. While constitutively expressed IRF8-dependent genes contained only sites mediating basal IRF8/PU.1 recruitment, inducible IRF8-dependent genes contained variable combinations of constitutive and inducible sites. Overall, these data show at the genome scale how the same TF can be linked to constitutive and inducible gene regulation via distinct combinations of alternative DNA-binding sites.
|
| |
|
| Overall design |
Chromatin immuno-precipitations of transcription factors IRF8, IRF1, PU.1, STAT1, STAT2 and of H3 lysine 27 acetylated followed by multiparallel sequencing, performed in bone marrow-derived macrophages from wild type (WT) and BXH2/TyJ mice. Cells were treated with lipopolysaccharide (LPS) for 2 or 4 hours, or interferon b (IFNb) for 30 or 60 minutes, 2 or 4 hours, or left unstimulated.
|
| |
|
| Contributor(s) |
Mancino A, Termanini A, Barozzi I, Ghisletti S, Ostuni R, Prosperini E, Ozato K, Natoli G |
| Citation(s) |
25637355 |
| |
| Submission date |
Mar 24, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Alberto Termanini |
| E-mail(s) |
termanini@me.com
|
| Organization name |
Istituto Clinico Humanitas
|
| Lab |
Bioinformatic Unit
|
| Street address |
Via Manzoni, 113
|
| City |
Rozzano |
| State/province |
MI |
| ZIP/Postal code |
20089 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (53)
|
|
| This SubSeries is part of SuperSeries: |
| GSE56123 |
A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages. |
|
| Relations |
| BioProject |
PRJNA242509 |
| SRA |
SRP040494 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56121_RAW.tar |
10.1 Mb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...