DNA demethylation facilitates globin translation in myelodysplastic syndrome

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591397
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: MATSUI HIROTAKA 広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
• Co-Investigator(Kenkyū-buntansha): KANAI Akinori 広島大学, 原爆放射線医科学研究所, 助教 (60549567)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: エピゲノム / DNAメチル化 / 骨髄異形成症候群

Outline of Final Research Achievements

Abnormal epigenetic regulations have been shown to be involved in the pathogenesis and/or progression of myelodysplastic syndrome (MDS) and this characteristic of disease led to the introduction of DNA demethylating agents including Azacytidine and Aza-deoxycytidine (Aza-dC) for the clinical management of MDS. In this study, we characterized genes whose expressions are directly increased by Aza-dC using K562 cells, in which DNA demethylation induces hemoglobin (Hb) synthesis, as an experimental model. By analyzing changes in DNA methylation status and gene expression together with histone modification, we found that genes that are suppressed by promoter methylation but are ready to be transcribed will be activated by DNA demethylation. In addition, we elucidated a mechanism by which K562 cells produce Hb upon DNA demethylation.

Free Research Field

血液内科学