PTIP Promotes Chromatin Changes Critical for Immunoglobulin Class Switch Recombination | Zendy

J. Daniel | Zendy; Margarida A. Santos | Zendy; Zhibin Wang | Zendy; Chongzhi Zang | Zendy; Kristopher R. Schwab | Zendy; Mila Janković | Zendy; Darius Filsuf | Zendy; Hua-Tang Chen | Zendy; Anna Gazumyan | Zendy; Arito Yamane | Zendy; YoungWook Cho | Zendy; HongWei Sun | Zendy; Kai Ge | Zendy; Weiqun Peng | Zendy; Michel C. Nussenzweig | Zendy; Rafael Casellas | Zendy; Gregory R. Dressler | Zendy; Keji Zhao | Zendy; André Nussenzweig | Zendy

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PTIP Promotes Chromatin Changes Critical for Immunoglobulin Class Switch Recombination

Author(s) -

J. Daniel,

Margarida A. Santos,

Zhibin Wang,

Chongzhi Zang,

Kristopher R. Schwab,

Mila Janković,

Darius Filsuf,

Hua-Tang Chen,

Anna Gazumyan,

Arito Yamane,

YoungWook Cho,

HongWei Sun,

Kai Ge,

Weiqun Peng,

Michel C. Nussenzweig,

Rafael Casellas,

Gregory R. Dressler,

Keji Zhao,

André Nussenzweig

Publication year - 2010

Publication title -

science

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.1187942

Subject(s) - chromatin , microbiology and biotechnology , immunoglobulin class switching , histone , biology , h3k4me3 , nucleosome , histone h3 , genetics , gene , promoter , gene expression , antibody , b cell

Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical for DNA recombination and repair. Here, we showed that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at lysine 4 (H3K4me3) and transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus, leading to defective immunoglobulin class switching. We also showed that PTIP accumulation at DSBs contributes to class switch recombination (CSR) and genome stability independently of Igh switch transcription. These results demonstrate that PTIP promotes specific chromatin changes that control the accessibility of the Igh locus to CSR and suggest a nonredundant role for the MLL3-MLL4 complex in altering antibody effector function.

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