Modulation of mRNA Expression of a Novel Human Myeloid-Selective CCAAT/Enhancer Binding Protein Gene (C/EBPe)
نویسندگان
چکیده
Human C/EBPe is a newly cloned gene coding for a CCAAT/ mRNA. Nuclear run-off assays and half-life studies showed that accumulation of C/EBPe mRNA by 9-cis RA was due enhancer binding protein that may be involved in the regulation of myeloid differentiation. Our studies showed that levto enhanced transcription. Furthermore, this C/EBPe mRNA accumulation did not require synthesis of new protein facels of C/EBPe mRNA were markedly increased in NB4 cells (promyelocytic leukemia line), because they were induced tors because 9-cis RA induced C/EBPe mRNA accumulation in the absence of new protein synthesis. ATRA also induced by 9-cis retinoic acid (9-cis RA) to differentiate towards granulocytes. Accumulation of C/EBPe mRNA occurred as early expression of C/EBPe protein in NB4 cells, as shown by Western blotting. In contrast to the increase of C/EBPe in as 1 hour after exposure of NB4 cells to 9-cis RA (5 Ì 10 mol/L); and at 48 hours, levels were increased by 5.1-fold. 9-cis RA–mediated granulocytic differentiation, the DMSOinduced differentiation of HL-60 cells down the granulocytic Dose-response studies showed that 10 to 10 mol/L 9-cis RA (12 hours) resulted in peak levels of C/EBPe mRNA; but pathway was associated with an initial reduction of C/EBPe mRNA levels. In summary, we have discovered that expreseven 10 mol/L 9-cis RA increased levels of these transcripts. NB4 cells pulse-exposed (30 minutes) to all-trans sion of C/EBPe mRNA is markedly enhanced as the NB4 promyelocytes are induced by retinoids to differentiate toretinoic acid (ATRA), washed, and cultured (3 days) with either dimethylsulfoxide (DMSO) or hexamethylene bisacetwards granulocytes. This induction of C/EBPemRNA expression is transcriptionally mediated and occurs in the absence amide (HMBA) had a prominent increase in levels of C/EBPe mRNA and an increase in granulocytic differentiation, but of synthesis of additional protein factors. We suspect that the C/EBPe promoter/enhancer contains a retinoic acid-reexposure to either DMSO or HMBA alone had no effect on base levels of C/EBPe and did not induce differentiation. sponse element that is directly stimulated by retinoids. q 1997 by The American Society of Hematology. Macrophage-differentiation of NB4 reduced levels of C/EBPe
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