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) gen e 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 a rea 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 Sp 1 as well as Sp3 to transactivate the promoter. This transactivation is med iated through adjacent binding sites rather than through the more distant S p binding site, suggesting a possible direct interaction between PU.1 and S p1/3. 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, suggesti ng that Sp3 acts as a positive regulator of Btk in vivo in the absence of S p1. (C) 1999 Academic Press.