Nuclear factor, erythroid 4 (NFE4)

Nuclear factor, erythroid 4 (NFE4) is an erythroid-specific transcription factor that forms part of the stage selector protein (SSP) complex with CP2, a ubiquitously expressed transcription factor[1][6][9]. NFE4 plays a crucial role in the regulation of hemoglobin gene switching, mediating preferential expression of gamma-globin genes in fetal erythroid cells and thus influencing fetal hemoglobin levels[1][2][3][9]. Alternative translation initiation produces two isoforms of NFE4: the long (22 kDa) isoform acts as an activator of gamma-globin gene expression, while the short (14 kDa) isoform represses this expression[1][4]. NFE4 is primarily expressed in fetal liver, cord blood, and bone marrow, as well as in K562 and HEL cell lines that express fetal globin genes[3]. Altered function or regulation of NFE4 is implicated in aberrant globin gene expression, relevant to various hemoglobinopathies and disorders of erythroid differentiation[3].

Other names

Transcription factor NF-E4NF-E4p22 NF-E4Fetal globin activator NF-E4Gamma-globin gene activator

Not directly targeted by drugs; mechanism would involve modulation of globin gene expression if targeted