Pluto Bioinformatics

GSE118794: The Chromatin Reader ZMYND8 Regulates Igh Enhancers to Promote Immunoglobulin Class Switch Recombination

Bulk RNA sequencing

Class Switch Recombination (CSR) is a DNA recombination reaction that diversifies the effector component of antibody responses. CSR is initiated by activation-induced cytidine deaminase (AID), which targets transcriptionally active immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3 Igh super-enhancer, 3 Regulatory Region (3RR), is essential for acceptor region transcription, but how this function is regulated is unknown. Here we identify the chromatin reader ZMYND8 as an essential regulator of the 3RR and CSR. In B cells, ZMYND8 binds promoters and super-enhancers, including the 3RR, and controls its activity by modulating the enhancer transcriptional status. In its absence, there is increased 3RR polymerase loading, and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, which is also dependent on the 3RR. Thus ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3 Igh super-enhancer. SOURCE: Thiago,Y,Oliveira (toliveira@rockefeller.edu) - Laboratory of Molecular Immunology The Rockefeller University