期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 19, 页码 7784-7789出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1305859110
关键词
AID; SSRP1
资金
- Global Centers of Excellence program of the Ministry of Education, Culture, Sports, Science, and Technology of Japan
- [17002015]
- [24590352]
- Grants-in-Aid for Scientific Research [22000015, 24590352] Funding Source: KAKEN
Somatic hypermutation (SHM) requires not only the expression of activation-induced cytidine deaminase, but also transcription in the target regions. However, how transcription guides activation-induced cytidine deaminase in targeting SHM to the Ig genes is not fully understood. Here, we found that the facilitates chromatin transcription (FACT) complex promotes SHM by RNAi screening of transcription elongation factors. Furthermore, FACT and histone H3.3, a hallmark of transcription-coupled histone turnover, are enriched at the V(D)J region, 5' flanking sequence of the S mu switch region and the light chain J kappa 5 segment region in the Ig loci. The regions with the most abundant deposition of FACT and H3.3 were also the most efficient targets of SHM. These results demonstrate the importance of histone-exchanging dynamics at the chromatin of SHM targets, especially in Ig genes.
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