DNA-binding and regulatory properties of the transcription factor and putative tumor suppressor p150(Sal2)

Abstract

The product of the SALL2 protein p150(Sal2) is a multi-zinc finger transcription factor with growth arrest and proapoptotic functions that overlap those of p53. Its DNA-binding properties are unknown. We have used a modified SELEX procedure with purified p150(Sal2) and a pool of oligonucleotides of random sequence to identify those that are bound preferentially by p150(Sal2). The consensus sequence for optimal binding in vitro is GGG(T/C)GGG, placing p150(Sal2) among a large group of GC box-binding proteins including the Sp1 family of transcription factors. A triple zinc finger motif in p150(Sal2) similar to that in Sp1 is required for DNA binding. p150(Sal2) and Sp1 show evidence of co-operative binding in vitro and of interaction in vivo. p150(Sal2), a known activator of the CDK inhibitor p21(Cip1/Waf1) (p21), binds to regions of the human p21 promoter that contain variations of the consensus sequence in multiple copies. p150(Sal2) is also shown to bind to the BAX promoter with similar elements and to activate its expression following an apoptotic stimulus. These results demonstrate binding of p150(Sal2) to two natural promoters with GC elements related to the optimal binding sequence defined in vitro and whose regulation is important for suppression of tumor growth. (C) 2011 Published by Elsevier B.V.