INCREASED EXPRESSION OF ACETYLCHOLINESTERASE T AND R TRANSCRIPTS DURING HEMATOPOIETIC DIFFERENTIATION IS ACCOMPANIED BY PARALLEL ELEVATIONSIN THE LEVELS OF THEIR RESPECTIVE MOLECULAR-FORMS

Differentiation of hematopoietic cells is known to be accompanied by p rofound changes in acetylcholinesterase (AChE) enzyme activity, yet th e basic mechanisms underlying this developmental regulation remain unk nown, We initiated a series of experiments to examine the molecular me chanisms involved in regulating AChE expression during hematopoiesis, Differentiation of murine erythroleukemia (MEL) cells using dimethyl s ulfoxide resulted in a 5- and 10-fold increase in intracellular and se creted AChE enzyme activity, respectively, Interestingly, these increa ses resulted from a preferential induction of the globular molecular f orm G(1) and a slight increase in G(4) instead of an increase in the l evels of the G(2) membrane-bound form, a molecular form expressed in m ature erythrocytes, Concomitantly, expression of the two predominant A ChE transcripts (R and T, for read-through and tail, respectively) in MEL cells was induced to a similar extent with differentiation. Nuclea r run-on assays performed with nuclei isolated from induced versus uni nduced MEL cells revealed that in contrast to the large increases seen in the transcription of the beta-globin gene, the transcriptional act ivity of the AChE gene remained largely unaffected after differentiati on. Determination of the half-lives of the R and T transcripts demonst rated that they both exhibited an increase in stability in induced MEL cells. Taken together, results from these studies indicate that postt ranscriptional regulatory mechanisms account for the increased express ion of AChE in differentiated hematopoietic cells.