Human HMG box transcription factor HBP1: a role in hCD2 LCR function

The locus control region (LCR) of the human CD2 gene (hCD2) confers T cell- specific, copy-dependent and position-independent gene expression in transg enic mice. This LCR consists of a strong T cell-specific enhancer and an el ement without enhancer activity (designated HSS3), which is required for pr evention of position effect variegation (PEV) in transgenic mice. Here, we identified the HMG box containing protein-1 (HBP1) as a factor binding to H SS3 of the hCD2 LCR, Within the LCR, HBP1 binds to a novel TTCATT-CATTCA se quence that is higher in affinity than other recently reported HBP1-binding sites. Mice transgenic for a hCD2 LCR construct carrying a deletion of the HBP1-binding sequences show a propensity for PEV if the transgene integrat es in a heterochromatic region of the chromosome such as the centromere or telomere. We propose that HBP1 plays an important role in chromatin opening and remodelling activities by binding to and bending the DNA, thus allowin g DNA-protein and/or protein-protein interactions, which increase the proba bility of establishing an active locus.