The mechanism that drives the switch from fetal to adult hemoglobin (Hb) provides a therapeutic target for β-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 β 0 /β 0 -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 β-hemoglobinopathies.
Keyphrases
- transcription factor
- long noncoding rna
- poor prognosis
- dna binding
- dna methylation
- end stage renal disease
- circulating tumor
- long non coding rna
- genome wide identification
- gene expression
- ejection fraction
- binding protein
- newly diagnosed
- single molecule
- chronic kidney disease
- cell free
- single cell
- cell proliferation
- peritoneal dialysis
- oxidative stress
- patient reported outcomes
- diabetic rats
- young adults
- endothelial cells
- nucleic acid
- drug induced