Sense and Anti-sense Transcription in the Murine c-myb Attenuator Region

Abstract

The c-myb proto-oncogene has been found to be expressed at high levels predominantly in normal tissues and tumor cell lines of immature hematopoietic origin (Westin 1982; Gonda 1982; Duprey 1985; Bender 1987a). In each lineage which has been examined expression of c-myb mRNA has been found to decrease during maturation. Recent evidence suggests, at least in the T cell lineage, that expression of c-myb mRNA may switch from high constitutive expression in immature T cells to a cell cycle related mode of expression at more mature stages of development (Thompson 1986; Reed 1986). These findings have suggested that the c-myb gene product may play a role in hematopoietic maturation and that down-regulation of c-myb expression is required for normal development to proceed. Indeed, transfection experiments have demonstrated that constitutive expression of myb may interfere with differentiation in tsE26 transformed monocytic cells and the inducible differentiation of murine erythroleukemia cells (Beug 1987; Clarke 1988). We have begun to examine how c-myb steady state mRNA levels are determined in a series of murine B lymphoid tumors which demonstrate developmentally regulated expression of c-myb mRNA levels. In these tumor cell lines, pre-B cell lymphomas contain 10 to greater than 100 times as much c-myb mRNA than B cell lymphomas or plasmacytomas (Bender 1987a). We find that these differences in steady state c-myb mRNA levels are regulated primarily by a block to transcription elongation which occurs in the first intron of the c-myb locus (Bender 1987b).