Isolation and characterization of BEN, a member of the TFII-I family of DNA-binding proteins containing distinct helix-loop-helix domains

The transcriptional regulation of the Hoxc8 gene is controlled during early mouse embryogenesis by an enhanceosome-like control region, termed the ear ly enhancer (EE), located 3 kb upstream from the Hoxc8 translation start si te. The EE is involved in establishing the posterior expression pattern of Hoxc8 at embryonic day (E) 8.5-9.0. Genetic and biochemical data have shown that nuclear factors interact with this region in a sequence-specific mann er. We have used a yeast one-hybrid screen in a search for transcription fa ctors that bind to EE motifs and have isolated a novel murine DNA-binding p rotein, termed BEN (binding factor for early enhancer). The ORF of BEN enco des a protein of 1072 amino acids and contains six helix-loop-helix domains , a hydrophobic leucine zipper-like motif, and a serine-rich repeat. The mu rine BEN gene is structurally similar to the human gene TFII-I in that both genes encode unique 95-amino acid long helix-loop/span-helix domains. The BEN gene produces several major transcripts (3.6, 4.4, and 5.9 kb) present in most adult tissues and shows discrete spatial and temporal domains of ex pression in areas of epithelial-mesenchymal interaction during mouse embryo genesis from E9.5 to E12.5. Several BEN-encoded polypeptides of different s izes ranging from 165 to 40 kDa were identified by Western blot analysis us ing BEN-specific polyclonal Abs. We propose, on the bases of sequence homol ogy, that BEN is the mouse ortholog of the recently described human gene, W BSCR11, known also as GTF2IRD1, GTF3, Cream1, and MusTRD1. This gene is del eted hemizygously in individuals with Williams Syndrome, an autosomal domin ant genetic condition characterized by complex physical, cognitive, and beh avioral traits resulting from a perturbed developmental process.