Histone methyltasferase links transcription to DNA repair.

2015 Fiscal Year Final Research Report

• Project Area: Coupling of replication, repair and transcription, and their common mechanism of chromatin remodeling
• Project/Area Number: 22131003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Chiba University (2014-2015); Osaka University (2010-2013)
• Principal Investigator: Kiyoe Aota (浦聖恵) 千葉大学, 理学(系)研究科(研究院), 教授 (80289363)
• Project Period (FY): 2010-04-01 – 2016-03-31
• Keywords: ヒストンメチル化 / 転写 / DNA損傷修復 / B細胞分化 / H3K36me / Whsc1

Outline of Final Research Achievements

Histone H3 di/trimethylation at lysine 36 (H3K36me2/3) is associated with actively transcribed regions, however, the control mechanisms and functions of H3K36me in higher eukaryotes are still enigmatic.
We found that H3K36 methyltransferase Wolf-Hirschhorn syndrome candidate 1 (WHSC1) associates with not only transcription factors but also DNA-damage response factors without exogenous DNA-damage, suggesting molecular coupling between transcription and DNA repair. Non-competitive reconstitution of hematopoietic cell analysis reveals that Whsc1 is required for normal B-cell development in vivo. The absence of Whsc1 partially blocks V(D)J recombination and induces apoptosis during early B-cell development. p53-deficiency rescues abnormal B-cell differentiation from Whsc1-/- hematopoietic stem cells. Based on these results we propose that Whsc1 links transcription and DNA damage repair for maintenance of genome integrity.

Free Research Field

分子生物学