Transcription coupled chromatin regulation in AID induced genome rearrangement

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: BEGUM NasimAra 京都大学, 医学(系)研究科(研究院), 准教授 (80362507)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: AID / SHM / CSR / H3K4me3 / FACT / SPT6 / BRD4 / UNG

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.

Free Research Field

Immunology and Genomics