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Status |
Public on Jun 08, 2015 |
Title |
Batf3 maintains Irf8 autoactivation for commitment of a novel clonogenic progenitor of CD8+DCs |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
Summary |
The transcription factors Batf3 and IRF8 are required for development of CD8α+ conventional dendritic cells (cDCs), but the basis for their actions was unclear. Here, we identify two novel Zbtb46+ progenitors that separately generate CD8α+ and CD4+ cDCs and arise directly from the common DC progenitor (CDP). Irf8 expression in the CDP depends on prior PU.1-dependent autoactivation, and specification of pre-CD8 DC progenitors requires IRF8 but not Batf3. However, upon pre-CD8 DC specification, Irf8 autoactivation becomes Batf3-dependent at a CD8α+ cDC-specific enhancer containing multiple AP1-IRF composite elements (AICEs) within the Irf8 superenhancer. CDPs from Batf3-/- mice that specify toward pre-CD8 DCs fail to complete CD8α+ cDC development due to decay of Irf8 autoactivation, and divert to the CD4+ cDC lineage.
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Overall design |
Examination of histone modifications (H3K27ac and H3K4me1) and 2 transcription factors (Batf3 and Irf8) and the p300 co-factor binding in 3 different dendritic cell subsets
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Contributor(s) |
Iwata A, Murphy KM |
Citation(s) |
26054719 |
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Submission date |
Mar 13, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Gary E Grajales-Reyes |
E-mail(s) |
grajalesg@wusm.wustl.edu
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Organization name |
Washington University in St. Louis
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Department |
Immunology
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Lab |
Dr. Kenneth Murphy
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Street address |
Room 7766, CSRB
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City |
St Louis |
State/province |
Mo |
ZIP/Postal code |
63110 |
Country |
USA |
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Platforms (1) |
GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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Samples (14)
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Relations |
BioProject |
PRJNA278283 |
SRA |
SRP056164 |