We have isolated and characterized seven members of the alpha 2u-globulin gene family from a rat genomic library. The 5' upstream region (up to 1250 base pairs starting from the EcoRI site in exon 2) of three clones was sequenced. The major transcriptional start points were located 25 base pairs downstream from the 'TATA' box. A very high degree of homology was observed over the entire studied region. Two of the examined genes displayed structural features which suggest that their expression may be impeded. A high degree of homology was observed between the promotor regions of alpha 2u-globulin and those of the major urinary protein (MUP) multigene family of the mouse. A remarkable feature is the variable length of an A-rich region between the putative 'CAAT' and the 'TATA' consensus sequences. The size of this region differs markedly between MUP and alpha 2u-globulin and between different members of the alpha 2u-globulin gene family. Comparison of the alpha 2u-globulin promotor with the corresponding region of other androgen-dependent genes (the C1, C2 and C3 subunits of prostatic steroid binding protein) reveals the presence of an A-rich region of homology located approximately 378 base pairs upstream from the cap site in the alpha 2u-globulin genes. This region compares well with a sequence of putative enhancer function previously demonstrated in the alpha-fetoprotein promotor and in the immunoglobulin heavy chain promoter.
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