ZBTB48 is a pioneer factor regulating B-cell-specific CIITA expression [RNA-seq]

CIITA is the master regulator of MHC II gene expression and hence the adaptive immune response. CIITA expression itself is tightly regulated by three cell type-specific promoters, pI, pIII, and by pIV. Here, we demonstrate that the telomere-binding protein and transcriptional activator ZBTB48 directly binds to both the critical activating elements within CIITA pIII and is essential for its gene expression. ZBTB48 establishes open chromatin at CIITA pIII upstream of activating H3K4me3 modifications both priming CIITA transcription for IFNg-induction and ensuring constitutive expression in primary murine B cells. Hence, ZBTB48 acts as a molecular on-off-switch for B-cell-specific CIITA expression. To comprehensively interrogate the effect of ZBTB48 on transcription upon IFNγ stimulation in U2OS cells using five WT and ZBTB48 KO clones each. Each of the five U2OS WT and ZBTB48 KO clones were treated with 250U/ml IFNγ for 24 hours. We globally analysed expression differences in our RNA-seq data comparing the five WT and ZBTB48 KO clones as biological replicates.