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

Contributors : Ver ónica Delgado-Benito ; Daniel B Rosen ; Qiao Wang ; Anna Gazumyan ; Joy Pai ; Thiago Y Oliveira ; Devakumar Sundaravinayagam ; Wenzhu Zhang ; Matteo Andreani ; Lisa Keller ; Kyong-Rim Kieffer-Kwon ; Aleksandra Pekowska ; Seolkyoung Jung ; Madlen Driesner ; Roman I Subbotin ; Rafael Cas ellas ; Brian T Chait ; Michel C Nussenzweig ; Michela Di VirgilioSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing ; OtherOrganism : Mus musculusClass 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 (3’RR), 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 3’RR and CSR. In B cells, ZMYND8 binds promoters and super-enhancers , including the 3’RR, and controls its activity by modulating the enhancer transcriptional status. In its absence, there is increased 3’RR polymerase loading, and decreased acceptor region transcription and CSR. In addition to CSR, ZMYND8 deficiency impairs somatic hypermutation (SHM) of Igh, wh ich is also dependent on the 3’RR. Thus ZMYND...

Source: GEO: Gene Expression Omnibus - October 4, 2018 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other Mus musculus Source Type: research