北海道支部について

DNAメチル化を介したレトロトラスポゾン抑制メカニズムの新たな側面

古関　明彦　先生

理化学研究所　統合生命医科学研究センター・副センター長

免疫器官形成グループ・グループディレクター

平成２６年６月３０日　１７時００分〜１８時００分

北海道大学 理学部７号館３階　７－３－１０号室

（札幌市北区北１０条西８丁目）

生命分子化学セミナー

日本生化学会北海道支部

Transient association of NP95 into nascent hemimethylated CpGs at

replication foci constitutes a key step for DNMT1 mediated maintenance DNA

methylation in mammals. Here, we reveal that protracted binding of NP95 to

hemimethylated sites has an unexpected role for disrupting transcriptional

silencing of CpG-rich proviral sequences in the mouse genome.  Exploiting

conditional deletions of Dnmt1 and Np95, we show that in Dnmt1-ablated cells

undergoing passive demethylation, NP95 is required for activation of IAP

(intracisternal A particle) endogenous retrotransposons (ERVs), while, in

Np95-ablated cells, the same ERVs remain silenced, despite acute

demethylation. Furthermore, we demonstrate that in the absence of NP95, the

H3K9 methyltransferase SETDB1 maintains IAP silencing, while in the absence

of DNMT1, prolonged binding of NP95 to hemimethylated DNA disrupts

SETDB1-dependent deposition of H3K9me3. Taken together, our observations

reveal that the fidelity of histone methylation-dependent proviral silencing

is dependent upon timely maintenance DNA methylation.

北海道大学大学院理学研究院化学部門

　　村上 洋太

TEL:　011-706-3813

e-mail: yota@sci.hokudai.ac.jp