| Budget Amount *help |
¥47,710,000 (Direct Cost: ¥36,700,000、Indirect Cost: ¥11,010,000)
Fiscal Year 2015: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2014: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2013: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2012: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2011: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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| Outline of Final Research Achievements |
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 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 ERV 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.
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