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 lambda light chain lambda(2-4) enhancer element, suggesting that SPI-C could act both as a positive and negative transcriptional regulator during B-lymphocyte differentiation.
Section for Immunology, CMB, Lund University, BMC I:13, 22184, Lund, Sweden. robert.carlsson@immuno.lu.se
Robert
R
Carlsson
Christine
C
Persson
Tomas
T
Leanderson
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001665:Binding Sites; D019556:COS Cells; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050835:Interferon Regulatory Factors; D008264:Macrophages / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D013234:Stem Cells / Q000276:immunology; D013997:Time Factors; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D000099218:Interferon Regulatory Factor-4
D001224:Aspartic Acid; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D015534:Trans-Activators; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C423918:Spic protein, mouse