Synergistic activation of the human Btk promoter by transcription factors Sp1/3 and PU.1

Analysis of the human Bruton's agammaglobulinemia tyrosine kinase (Btk) gene promoter revealed that 280 bp upstream of the transcriptional start site is sufficient for a cell restricted expression pattern. Here, the interplay of the transcription factors Sp1, Sp3, and PU.1 binding to this promoter area was analysed. All three proteins are able to independently activate the promoter in Drosophila Schneider (SL2) cells lacking endogenous Sp- or PU.1-like activities. Furthermore, PU.1 is able to act synergistically with Sp1 as well as Sp3 to transactivate the promoter. This transactivation is mediated through adjacent binding sites rather than through the more distant Sp binding site, suggesting a possible direct interaction between PU.1 and Sp1/3. Expression of Etk was found in ES cells and levels of expression were the same as in ES cells with a targeted deletion of the Sp1 gene, suggesting that Sp3 acts as a positive regulator of Btk in vivo in the absence of Sp1. (C) 1999 Academic Press.