Regulation of BCL11A DNA binding and expression in human erythrocyte precursor HUDEP-2 cells - PubMed
3 hours ago
- #hemoglobin
- #epigenetics
- #BCL11A
- BCL11A is a transcription factor important for neurodevelopment and hematopoiesis, regulating the switch from fetal to adult hemoglobin.
- BCL11A has multiple isoforms (L and XL) with distinct DNA-binding domains (ZF2-3 and ZF4-6), recognizing the 6-bp motif TGNCCA with specific strand interactions.
- Epigenetic inhibitors targeting DNA methylation and histone modifications in HUDEP-2 cells increased fetal hemoglobin (HbF) expression, with FTX6058 notably reducing BCL11A levels.
- A screen of 213 pomalidomide-derived compounds identified four that decreased levels of zinc-finger proteins IKZF1 and ZFP91 without altering BCL11A directly.
- The study provides insights into BCL11A DNA binding, epigenetic regulation, and small-molecule effects, offering new therapeutic strategies for HbF reactivation.