INDUCTION OF THE CD11B GENE DURING ACTIVATION OF THE MONOCYTIC CELL-LINE U937 REQUIRES A NOVEL NUCLEAR FACTOR MS-2

The differentiation of myeloid precursors into mature myelomonocytic c ells is characterized by the induction of the gene encoding the beta(2 ) integrin CD11b. The transcription factors Sp1 and PU.1 prime the CD1 1b promoter, but the nature of the factors responsible for its inducib le expression are unknown. In addition to the CD11b gene, the homologo us genes encoding CD11a and CD11c also exhibit inducible expression du ring myeloid differentiation. Therefore, we compared the nucleotide se quences of the CD11a, CD11b, and CD11c gene promoters to identify comm on elements that might contribute to inducible expression. This analys is identified one such element repeated four times within the CD11b pr omoter. Mutation of these elements indicated that two, MS-2 beta and M S-2 gamma, are critical to the induction of the CD11b gene during diff erentiation of the pro-monocytic cell line U937. Electrophoretic mobil ity shift assays indicate that MS-2 beta and MS-2 gamma interact with nuclear factors that are induced during U937 differentiation. These fa ctors are detected at the time the CD11b promoter is activated. The mo lecular mass of these factors is approximately 28 kDa, and their DNA b inding characteristics are indistinguishable from those of the novel n uclear factor MS-2. Taken together, our data indicate that MS-2 mediat es induction of the CD11b gene as cells of the monocytic lineage matur e. The presence of multiple potential binding sites for MS-2 in the pr omoter regions of a wide range of genes expressed in mature myeloid ce lls suggests this factor plays a general role in myeloid differentiati on.