期刊
NATURE COMMUNICATIONS
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms2823
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [22021036]
- Japan Society for the Promotion of Science [23390122, 24659224, 22590436]
- Global-COE program (Global Education and Research Centre Aiming at the control of AIDS, Kumamoto University)
- program for Promotion of Fundamental Studies in Health Sciences
- US National Institutes of Health [ES13192, GM21422]
- Third-Term Comprehensive Control Research for Cancer and Research on Biological Markers for New Drug Development
- Grants-in-Aid for Scientific Research [23390122, 22021036, 24659224, 22590436] Funding Source: KAKEN
Somatic hypermutation in B cells is initiated by activation-induced cytidine deaminase-catalyzed C -> U deamination at immunoglobulin variable regions. Here we investigate the role of the germinal centre-associated nuclear protein (GANP) in enhancing the access of activation-induced cytidine deaminase (AID) to immunoglobulin variable regions. We show that the nuclear export factor GANP is involved in chromatin modification at rearranged immunoglobulin variable loci, and its activity requires a histone acetyltransferase domain. GANP interacts with the transcription stalling protein Spt5 and facilitates RNA Pol-II recruitment to immunoglobulin variable regions. Germinal centre B cells from ganp-transgenic mice showed a higher AID occupancy at the immunoglobulin variable region, whereas B cells from conditional ganp-knockout mice exhibit a lower AID accessibility. These findings suggest that GANP-mediated chromatin modification promotes transcription complex recruitment and positioning at immunoglobulin variable loci to favour AID targeting.
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