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E-GEOD-75930 - A PTIP-PA1 subcomplex promotes transcription for IgH class-switching independently from the associated MLL3/MLL4 methyltransferase complex

Status
Released on 12 December 2015, last updated on 19 December 2015
Organism
Mus musculus
Samples (4)
Protocols (2)
Description
Class-switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B cell genome. Transcription at the immunoglobulin heavy-chain (Igh) locus targets CSRassociated DNA damage and is promoted by the BRCT domain-containing PTIP protein. Although PTIP is a unique component of the MLL3/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear. Here we dissect the minimal structural requirements of PTIP and its different protein complexes using quantitative proteomics in primary lymphocytes. We find that PTIP functions in transcription and CSR separately from its association with the MLL3/MLL4 complex and from its localization to sites of DNA damage. We identify a tandem BRCT domain of PTIP that is sufficient for CSR and identify PA1 as its main functional protein partner. Collectively, we provide genetic and biochemical evidence that a PTIP-PA1 subcomplex functions independently from the MLL3/MLL4 complex to mediate transcription during CSR. These results further our understanding of how multi-functional chromatin-modifying complexes are organized by subcomplexes that harbor unique and distinct activities. Genome-wide analysis of histone modifications in PA1-WT and -KO mouse activated B cells
Experiment type
ChIP-seq 
Contacts
Jeremy Daniel <jeremy.daniel@cpr.ku.dk>, Andrea Vala, Andreas Mund, André Nussenzweig, Blanca López-Méndez, Brian T Weinert, Chunaram Choudhary, Dan Su, Guillermo Montoya, Irina Pozdnyakova, Jeremy A Daniel, Ji-Eun Lee, Joan Yuan, Kai Ge, Laura M Pikkupeura, Linda M Starnes, Margarida A Santos, Martina K Højfeldt, Rebeca Soria, Weiqun Peng, Wenjing Yang, Young-Wook Cho
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Investigation descriptionE-GEOD-75930.idf.txt
Sample and data relationshipE-GEOD-75930.sdrf.txt
Processed data (1)E-GEOD-75930.processed.1.zip
Links