SPI-C, a PU-box binding ETS protein expressed temporarily during B-cell development and in macrophages, contains an acidic transactivation domain located to the N-terminus

Mice deficient for SPI-group ETS transcription factors PU.1 or SPI-B fail to generate lymphocytes or do not mount normal antibody mediated immune responses, respectively. PU.1 expression is restricted to B-, T-lymphocytes and macrophages, while SPI-B is expressed in B- and T-lymphocytes. SPI-C is an ETS transcription factor closely related to PU.1 and SPI-B, and expressed temporarily during B-cell development and in macrophages. By deletion and mutation analysis we show that the SPI-C protein has a transactivation domain located to the N-terminus, and that the transactivation activity is reduced to that of the DNA binding domain (DBD) alone when four aspartic acid residues are mutated to alanines. PU.1 and SPI-B regulate transcription from acidic domains located to the N-terminus and by recruiting the co-activator PIP to adjacent sites in a sequence specific manner. In contrast to PU.1 and PIP, SPI-C and PIP were unable to form a distinct ternary complex on the Ig λ light chain λ2–4 enhancer element, suggesting that SPI-C could act both as a positive and negative transcriptional regulator during B-lymphocyte differentiation.