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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
PU.1 level-directed chromatin structure remodeling at the Irf8 gene drives dendritic cell commitment
Jörg Schönheit1, Christiane Kuhl, Marie Luise Gebhardt
1Max Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Cell Reports
|April 30, 2013
Summary
The transcription factor PU.1 guides dendritic cell (DC) development by remodeling chromatin at the interferon regulatory factor 8 (Irf8) gene. This process is crucial for DC lineage commitment, preventing alternative myeloid cell fates.
Area of Science:
- Immunology
- Cell Biology
- Genetics
Background:
- Dendritic cells (DCs) are critical immune regulators.
- Transcriptional control of DC lineage commitment remains unclear.
Purpose of the Study:
- To elucidate the transcriptional mechanisms governing dendritic cell (DC) lineage commitment.
- To identify the role of the PU.1 transcription factor in DC fate determination.
Main Methods:
- Utilized an Irf8 reporter mouse model to track early DC progenitors.
- Investigated chromatin structure remodeling at the Irf8 gene.
- Analyzed the impact of PU.1 levels on Irf8 expression and myeloid lineage choice.
Main Results:
- PU.1 induces higher-order chromatin remodeling at the Irf8 gene, initiating DC fate.
- Irf8 is essential for DC commitment, preventing reprogramming to neutrophils.
- High PU.1 levels drive myeloid Irf8 expression via chromosomal looping and enhancer activation.
Conclusions:
- PU.1 acts as a concentration-dependent regulator of myeloid lineage selection.
- Specific chromatin remodeling at the Irf8 gene dictates DC differentiation.
- DC commitment requires an active, Irf8-dependent pathway to escape alternative myeloid fates.
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