ZBTB48 is a pioneer factor regulating B-cell-specific CIITA expression [FAIRE-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 pioneering function of ZBTB48 at promoters in U2OS cells using two WT and ZBTB48 KO clones each. Formaldehyde assisted isolation of regulatory elements DNA-sequencing (FAIRE-seq) was performed in two U2OS WT and ZBTB48 KO clones each were treated with 250U/ml IFN? for 24 hours. Open chromatin was interogated in the two WT and ZBTB48 KO clones, specifically at promoters bound by ZBTB48.