DIFFERENTIATION-DEPENDENT EXPRESSION OF A HUMAN CARBOXYLESTERASE IN MONOCYTIC CELLS AND TRANSCRIPTION FACTOR-BINDING TO THE PROMOTER

Carboxylesterases play an important role in defense and clearance mech anisms of the monocyte/macrophage system. During the differentiation p rocess of cells from the monocytic cell line THP-1 we observed a trans ient transcriptional upregulation of a human carboxylesterase analyzed by means of Northern blots. In PMA-treated THP-1 cells we could detec t three major transcription initiation sites as revealed by Nuclease P rotection Assay carried out with two overlapping antisense RNA probes. We have recently cloned the carboxylesterase upstream sequence and sh owed its basal promoter activity in CHO cells. Using electrophoretic m obility shift analysis we demonstrated that the promoter region spanni ng base pairs -1 to -275, which contains several putative binding site s for transcription factors, is bound by nuclear factors Spl and IRBP but not by C/EBPs. Taken together these data indicate that carboxylest erase gene transcription in THP-1 cells starts at multiple initiation sites and that Spl and IRBP may be critical factors for modulating the differentiation-dependent transcription of this human carboxylesteras e gene. (C) 1997 Academic Press