| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Outline of Final Research Achievements |
Accumulating evidence has demonstrated successful epigenetic therapy by targeting DNA demethylation with Aza/Aza-dC in MDS. However, the mechanism by which Aza/Aza-dC induces Hb synthesis is still largely unknown. To identify the direct targets of Aza-dC, we applied whole genome methylation and transcriptome analysis to K562 cells, in which Hb synthesis was significantly enhanced. This identified that a translational regulator, eEF1A2 was greatly induced by Aza-dC, coupled with significant DNA demethylation of the gene promoter. BMT assay using eEF1A2-deficient mice and ATAC-seq analysis, which identifies genome wide open chromatin regions revealed that the related eEF1A1 gene mainly contributes to hematopoiesis. These data indicated that the ectopic expression of eEF1A2 is a mechanism through which Aza-dC improves the anemia of MDS patients.
|
