期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 209, 期 11, 页码 2099-2111出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20112145
关键词
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资金
- CRUK
- SA Archimedes-Estonian Foundation of European Union Education and Research
- Marie Curie FP 7 fellowship
- la Ligue Contre le Cancer, France
- Agence Nationale pour la Recherche [ANR-07-MIME-004-01]
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Istituto FIRC di Oncologia Molecolare, Italy (IFOM)
Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.
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