Genomics

Dataset Information

300

Batf3 maintains Irf8 autoactivation for commitment of a novel clonogenic progenitor of CD8+DCs


ABSTRACT: 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. 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

ORGANISM(S): Mus musculus  

SUBMITTER: Gary E Grajales-Reyes   Kenneth M Murphy  Arifumi Iwata 

PROVIDER: E-GEOD-66899 | ArrayExpress | 2015-06-08

SECONDARY ACCESSION(S): SRP056164GSE66899PRJNA278283

REPOSITORIES: GEO, ArrayExpress, ENA

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