Basal transcription of the human TBX3 gene, a key developmental regulator which is overexpressed in several cancers, requires functional NF-Y and Sp1 sites

TBX3 is a member of the T-box family of genes that encode developmentally important transcription factors. Mutations resulting in decreased levels of functional TBX3 lead to Ulnar-Mammary Syndrome and increased levels of TBX3 have been linked to several cancers. To understand the mechanisms regulating TBX3 expression we have previously cloned the 5′-flanking region of the human TBX3 gene and here we describe cis-elements required for its basal transcription. Using site-directed mutagenesis, luciferase reporter assays and in vitro and in vivo DNA binding experiments we identify a Sp1 element and two CCAAT boxes to be essential for basal TBX3 promoter activity. Our results are consistent with reports that these sites are necessary for efficient basal transcription in genes which lack TATA boxes or an Initiator which we show to be the case for TBX3.