Functional analysis of the interplay between histone H2A phosphorylation and ubiquitylation

2015 Fiscal Year Final Research Report

• Project/Area Number: 26830127
• 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(医学系), 助教 (80587717)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: エピゲノム / ヒストン修飾 / 転写制御

Outline of Final Research Achievements

Recent studies have shown that functional dysregulation of histone modifications leads normal cells to malignant cancer statuses. Too many aberrant expressions, abnormal rearrangements, mutations of genes encoding chromatin modification are occurred in multiple cancer cell types. However, a few mutations of genes encoding histone proteins themselves are identified in patients. Existences of histone mutations in other variants and canonical histones, and their malignancies are largely unknown. Our goal is to demonstrate that the dysregulation of the interplay between phosphorylation of 120th threonine (T120-H2A) and mono-ubiquitylation (K119-H2A) within histone H2A C-terminus region triggers tumorigenesis. We found that phosphorylation of T120-H2A by VRK1 kinase upregulates expression of Cyclin D1. Deregulation of phosphorylation of T120-H2A by VRK1 kinase caused tumorigenesis. We also identified missense mutations of H2A that possess tumorigenic activity.

Free Research Field

生化学