|
| Status |
Public on Mar 02, 2017 |
| Title |
Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk [ChIP_narrow] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The M1 and the M2 macrophage polarization programs (activated by IFNγ and IL-4, respectively) lie at the opposite edges of a continuum of activation states but are frequently co-activated during co-infections and in cancer despite controlling divergent functional responses. Whether these two programs are mutually exclusive, how they influence each other, and whether one represents the prevailing response, are all open questions. Co-administration of IFNγ and IL-4 exerted complex inhibitory effects over the M1 and M2 programs at the level of both epigenomic and transcriptional changes. Computational data mining and validation analyses revealed the molecular basis of the differential sensitivity of genes and cis-regulatory elements to the antagonistic effects of the opposite stimulus. For instance, while STAT1 and IRF motifs were associated with robust and IL-4-resistant responses to IFNγ, their coexistence with binding sites for some auxiliary transcription factors such as AP-1, generated vulnerability to IL-4-mediated inhibition. These data provide a core mechanistic framework for the integration of signals that control macrophage activation and the starting point for understanding macrophage responses in complex environmental conditions
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| |
|
| Overall design |
Analysis of transcriptional and epigenomic changes in mouse macrophages stimulated with different cytokines or their combinations
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| |
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| Contributor(s) |
Piccolo V, Curina A, Genua M, Ghisletti S, Simonatto M, Sabò A, Amati B, Ostuni R, Natoli G |
| Citation(s) |
28288101 |
| |
| Submission date |
Jul 18, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Viviana Piccolo |
| E-mail(s) |
viviana.piccolo@ieo.it
|
| Organization name |
European Institute of Oncology (IEO)
|
| Department |
Department of Experimental Oncology
|
| Lab |
Gioacchino Natoli Lab
|
| Street address |
Via Adamello 16
|
| City |
Milano |
| State/province |
Milano |
| ZIP/Postal code |
20139 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
|
| Samples (22)
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| This SubSeries is part of SuperSeries: |
| GSE84520 |
Opposing macrophage-polarization programs show extensive epigenomic and transcriptional cross-talk |
|
| Relations |
| BioProject |
PRJNA329536 |
| SRA |
SRP078841 |
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