Induction of human fetal globin gene expression by a novel erythroid factor, NF-E4

The stage selector protein (SSP) is a heteromeric complex involved in prefe rential expression of the human gamma-globin genes in fetal-erythroid cells , We have previously identified the ubiquitous transcription factor CP2 as a component of this complex. Using the protein dimerization domain of CP2 i n a yeast two-hybrid screen, we have cloned a novel gene, NF-E4, encoding t he tissue-restricted component of the SSP, NF-E4 and CP2 coimmunoprecipitat e from extract derived from a fetal-erythroid cell line, and antiserum to N F-E4 ablates binding of the SSP to the gamma promoter, NF-E4 is expressed i n fetal liver, cord blood, and bone marrow and in the K562 and HEL cell lin es, which constitutively express the fetal globin genes. Enforced expressio n of NF-E4 in K562 cells and primary erythroid progenitors induces endogeno us fetal globin gene expression, suggesting a possible strategy for therape utic intervention in the hemoglobinopathies.