CAAT ENHANCER-BINDING PROTEINS ARE INVOLVED IN BETA-GLOBIN GENE-EXPRESSION AND ARE DIFFERENTIALLY EXPRESSED IN MURINE ERYTHROLEUKEMIA AND K562 CELLS/

Acting in cis with the beta-globin locus control region, the CAAT box of the beta-globin gene promoter stimulates transcription 10 fold in m urine erythroleukemia (MEL) cells but is without effect in K562 cells. Our previous studies suggested that of four proteins from MEL cells t hat bind to this CAAT box region (CP1, GATA-1, and two factors that we re denoted DSFr and DSF1) DSFr is involved in the up regulation of tra nscription. In the present report, the DSFr protein in MEL cells was i dentified as C/EBP gamma through expression cloning and antibody studi es, C/EBP gamma DNA binding activity could not be detected in K562 cel ls, However, K562 cells, but not MEL cells, were found to express LIP, which is a truncated form of C/EBP beta and is an inhibitor of transc ription, Thus, the differential expression of C/EBP members could acco unt for the ability of the beta-globin CAAT box to stimulate transcrip tion in MEL cells, but not function in K562 cells, Juxtaposing a speci fic C/EBP binding sequence next to the >beta-globin promoter, in const ructs in which the CAAT box had been rendered inactive by mutation or deletion, restored full promoter activity in MEL cells only if CP1 sti ll bound to the promoter, In conjunction with previous mutation analys es, these results suggest that C/EBP gamma may collaborate with CP1 to enhance transcription through the beta-globin CAAT box.