| First Author | Zhu X | Year | 2020 |
| Journal | Exp Biol Med (Maywood) | Volume | 245 |
| Issue | 15 | Pages | 1308-1318 |
| PubMed ID | 32715783 | Mgi Jnum | J:343935 |
| Mgi Id | MGI:6881578 | Doi | 10.1177/1535370220945305 |
| Citation | Zhu X, et al. (2020) NRF2 mediates gamma-globin gene regulation through epigenetic modifications in a beta-YAC transgenic mouse model. Exp Biol Med (Maywood) 245(15):1308-1318 |
| abstractText | IMPACT STATEMENT: Sickle cell disease is an inherited hemoglobin disorder that affects over 100,000 people in the United States causing high morbidity and early mortality. Although new treatments were recently approved by the FDA, only one drug Hydroxyurea induces fetal hemoglobin expression to inhibit sickle hemoglobin polymerization in red blood cells. Our laboratory previously demonstrated the ability of the NRF2 activator, dimethyl fumarate to induce fetal hemoglobin in the sickle cell mouse model. In this study, we investigated molecular mechanisms of gamma-globin gene activation by NRF2. We observed the ability of NRF2 to modulate chromatin structure in the human beta-like globin gene locus of beta-YAC transgenic mice during development. Furthermore, an NRF2/TET3 interaction regulates gamma-globin gene DNA methylation. These findings provide potential new molecular targets for small molecule drug developed for treating sickle cell disease. |
