2013 Fiscal Year Final Research Report

Analysis of the transcriptional mechanism regulated by H2A phosphorylation and ubiquitylation

Research Project

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
Keywords	エピゲノム / ヒストン修飾 / 転写制御
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.