| Project/Area Number |
24710216
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Genome biology
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
AIBARA HITOSHI 長崎大学, 医歯(薬)学総合研究科, 助教 (80587717)
|
|---|
| Project Period (FY) |
2012-04-01 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
|---|
| Keywords | エピゲノム / ヒストン修飾 / 転写制御 / エピジェネティクス / リン酸化 / ユビキチン化 / キナーゼ / ChIP-seq |
|---|
| Research Abstract |
We have found that 120th threonine of histone H2A (H2A-T120) is phosphorylated by VRK1 in human cancer cell lines. We have also demonstrated that H2A-T120 phosphorylation and mono-ubiquitylation of 119th lysine (H2A-K119) are mutually inhibitory and this mutual inhibition functions at transcriptional regulation in vitro. However, the existence of this mutual inhibition in vivo and the molecular mechanism are still unknown. In this study, we identified direct target genes that are activated by VRK1-mediated H2A-T120 phosphorylation, and are conversely repressed by H2A-K119 ubiquitylation. Overexpression of CyclinD1, one of these direct target genes, can rescue a growth defect caused by VRK1 knockdown. Our result suggest that transcriptional regulation of CyclinD1gene by VRK1-mediated H2A-T120 phosphorylation is a key regulator to control cell growth and trigger tumorigenesis.
|
