PLX311717

GSE156126: Temporal analysis of Brd4 displacement in the role of B cell survival, proliferation and differentiation

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

JQ1 is a BET-bromodomain inhibitor that has immunomodulatory effects. However, the precise molecular mechanism that JQ1 targets to elicit changes in antibody production isnot understood. Our results show that JQ1 induces apoptosis, reduces cell proliferation, and as a consequence, inhibits antibody secreting cell differentiation. ChIP-sequencing reveals a selective displacement of Brd4 in response to acute JQ1 treatment (<2 hours), resulting in specific transcriptional repression. After 8 hours, subsequent alterations in gene expression arose as a result of global loss of Brd4 occupancy. We demonstrate that apoptosis induced by JQ1 was solely attributed to the pro-apoptotic protein Bim (Bcl2l11). Conversely, cell cycle regulation by JQ1 was associated with multiple Myc-associated gene targets. Our results demonstrate that JQ1 drives temporal changes in Brd4 displacement that results in a specific transcriptional profile that directly affects B cell survival and proliferation to modulate the humoral immune response. SOURCE: Isabella Kong The Walter and Eliza Hall Institute of Medical Research