Screening for trans-acting factors and other factors involved in the activating or silencing of the gamma-globin gene during human ontogeny.

Researchers hope to increase gamma-globin expression by controlling potential trans-acting factors that specifically activate the gamma-globin gene in fetuses or silence this gene in adults to potentially treat sickle cell disease and beta-thalassemias. To characterize genes encoding such factors, we analyzed the differential expression of mRNAs in erythroid induction cultures of CD34+ cells derived from normal adult bone marrow, umbilical cord blood, and bone marrow from a patient with heterocellular hereditary persistence of fetal hemoglobin. Using differential-display - reverse-transcription PCR analysis, we identified a number of genes with differential expression in the above-mentioned cells. The differential expression of some genes was also confirmed by quantitative real-time PCR. Our data provide important clues for identifying and validating trans-activators that activate the gamma-globin gene in fetuses, and trans-acting factors involved in silencing the gamma-globin gene in adults.