Requirement of GATA-1 and p45 NF-E2 expression in butyric acid-induced erythroid differentiation

Butyric acid (BA) is known to induce overexpression of fetal hemoglobin and then erythroid differentiation. Therefore, BA is currently under clinical investigation as a potential therapy for the treatment of sickle cell disea se and cancer. Nevertheless, the molecular mechanisms involved in HA-induce d differentiation remain largely unknown. Previous reports have shown that BA-induced overexpression of erythroid genes occurred at the transcriptiona l level, suggesting the involvement of erythroid transcription factors. Her e, we intend to demonstrate the requirement of GATA-1 and NF-E2 transcripti on factors in the BA-induced erythroid differentiation of human leukemic K5 62 cells. Time-course experiments showed that nuclear levels of GATA-1 and p45 NF-E2 proteins increased during BA treatment. Moreover, antisense oligo deoxynucleotides targeting either GATA-1 or p45 NF-E2 proteins inhibited bo th protein expression and BA-induced differentiation. In contrast, BA-induc ed cell growth inhibition was not affected. These results provide the first direct evidence for the requirement of GATA-1 and NF-E2 in BA-induced diff erentiation process. (C) 1998 Academic Press.