ZBTB48 is a pioneer factor regulating B-cell-specific CIITA expression [ChIP-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. Overall design: To investigate the effect of loss of ZBTB48 on H3K4me3 activation mark at promoters regulated by ZBTB48 upon IFN? stimulation in U2OS cells using three WT and ZBTB48 KO clones each. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for histone modification H3K4me3 in each of the three U2OS WT and ZBTB48 KO clones treated with 250U/ml IFN? for 24 hours. We compared enrichment of H3K4me3 in the three WT and ZBTB48 KO clones as biological replicates, specifically at promoters bound by ZBTB48.