| RRC ID |
90143
|
| Author |
Bao X, Gao Y, Wang Z, Ye Y, Chen D, Zuo Y, Zhao C, Xu X.
|
| Title |
Activation of γ-globin expression by LncRNA-mediated ERF promoter hypermethylation in β-thalassemia.
|
| Journal |
Clin Epigenetics
|
| Abstract |
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 β0/β0-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.
|
| Volume |
16(1)
|
| Pages |
12
|
| Published |
2024-1-13
|
| DOI |
10.1186/s13148-023-01614-6
|
| PII |
10.1186/s13148-023-01614-6
|
| PMID |
38218889
|
| PMC |
PMC10787479
|
| MeSH |
Adult
DNA Methylation
Fetal Hemoglobin / genetics
Humans
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
Repressor Proteins / genetics
beta-Thalassemia* / genetics
beta-Thalassemia* / therapy
gamma-Globins / genetics
gamma-Globins / metabolism
|
| Resource |
| Human and Animal Cells |
HUDEP-2(RCB4557) |
