| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
AID is the key enzyme required for antibody gene diversification by mutation (SHM) and recombination (CSR). AID induced SHM and CSR of transcriptionally active Ig heavy chain locus (IgH) occur via complex DNA cleavage and recombination. The study aimed to explore transcription-coupled chromatin features involved in AID induced genomic rearrangements. It revealed that the AID target loci that undergo DNA break are enriched with SPT6, FACT, H3K4me3 and H3.3. While SPT6 and FACT like histone chaperones are required for the epigenetic integrity of the AID target loci, SPT6 is specifically required for the AID locus for its expression. Moreover, H4 acetyl reader BRD4 promoted recombination phase of CSR by recruiting critical DNA repair proteins, UNG and 53BP1. Therefore, target loci associated histone epigenetic marks and specialized chromatin proteins are playing important role in AID induced genomic instability regulation.
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