Activation of γ-globin expression by LncRNA-mediated ERF promoter hypermethylation in ß-thalassemia.
Clin Epigenetics
; 16(1): 12, 2024 01 13.
Article
em En
| MEDLINE
| ID: mdl-38218889
ABSTRACT
The mechanism that drives the switch from fetal to adult hemoglobin (Hb) provides a therapeutic target for ß-thalassemia. We have previously identified that hypermethylation of transcription factor ERF promoter reactivated γ-globin expression. To uncover the mechanism underlying the hypermethylation of ERF promoter, we performed RNA sequencing in ß0/ß0-thalassemia patients and identified an upregulated long noncoding RNA (RP11-196G18.23) associated with HbF production. RP11-196G18.23 bound to the ERF promoter and recruited DNA methyltransferase 3A to promote DNA hypermethylation-mediated ERF downregulation, thereby ameliorating ERF-induced γ-globin inactivation. The identification of RP11-196G18.23 provides an epigenetic mechanism for the reactivation of fetal γ-globin expression for ß-hemoglobinopathies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Talassemia beta
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article