NRF2 mediates γ-globin gene regulation through epigenetic modifications in a ß-YAC transgenic mouse model.
Exp Biol Med (Maywood)
; 245(15): 1308-1318, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32715783
ABSTRACT
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 γ-globin gene activation by NRF2. We observed the ability of NRF2 to modulate chromatin structure in the human ß-like globin gene locus of ß-YAC transgenic mice during development. Furthermore, an NRF2/TET3 interaction regulates γ-globin gene DNA methylation. These findings provide potential new molecular targets for small molecule drug developed for treating sickle cell disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Artificiais de Levedura
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Epigênese Genética
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Fator 2 Relacionado a NF-E2
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Gama-Globinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos