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SmallRNA-SEQ of mutants B cell for IgH 3'RR and Emu

ABSTRACT: SmallRNA-SEQ of mutants B cell for IgH 3'RR and Emu

ORGANISM(S): Mus musculus

PROVIDER: GSE90759 | GEO | 2017/06/13

SECONDARY ACCESSION(S): PRJNA355955

REPOSITORIES: GEO

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RNA-SEQ of mutants B cell for IgH 3'RR and Emu

Project description:RNA-SEQ of mutants B cell for IgH 3'RR and Emu

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Project description: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 (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, which is also dependent on the 3’RR. Thus ZMYND8 controls Igh diversification in mature B lymphocytes by regulating the activity of the 3’ Igh super-enhancer.

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Project description:RNA-SEQ of mutants B cell for IgH 3'RR and Emu

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