Altered expression of the developmentally regulated NFI gene family during phorbol ester-induced differentiation of human leukemic cells.

The nuclear factor I (NFI) family of transcription/replication proteins is required for the cell type-specific expression of a number of cellular and viral genes. There are four evolutionarily conserved NFI genes (NFI-A, -B, -C and -X) that encode DNA-binding proteins of similar or identical DNA-binding specificity. To address the role of this family of highly conserved transcription/replication proteins in cell differentiation and development, we have assessed the expression of NFI proteins (by DNA binding) and mRNAs of each of the four NFI genes during the in vitro differentiation of several human leukemic cell lines. These cell lines differ in their pattern of differentiation upon exposure to the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA). In K562 and OCI/AML-3 cells, the levels of the four NFI mRNAs and the mobility of NFI-DNA complexes present in nuclear extracts changed during treatment with TPA. The TPA-induced change in mobility of NFI-DNA complexes in OCI/AML-3 cells was blocked by an inhibitor of protein synthesis, cycloheximide. These changes in NFI protein and mRNA expression appear to be cell type-or lineage-specific since no changes were seen during the TPA-induced differentiation of HL-60 or U937 cells. These studies indicate that although their DNA-binding specificities are similar, the proteins encoded by the four NFI genes may differ in their biological functions and play distinct roles in hematopoietic development.