GENOMIC ORGANIZATION, CHROMOSOMAL LOCALIZATION AND PROMOTER FUNCTION OF THE HUMAN ZINC-FINGER GENE PAT133

We report the genomic structure and chromosomal localization of the human zinc-finger gene pA T133. This gene belongs to a family of four human immediate-early genes (pAT133, pAT225/EGR1, pAT591/EGR2 and EGR3), which have almost identical zinc-finger domains, but distinct flanking regions. The human pAT133 gene is organized in two exons, and has been mapped to human chromosome 2p13. We determined the transcription start site by primer extension analysis and identified several regulatory elements in the upstream regulatory sequence. The pAT133-promoter functions as an inducible promoter in human T cells and in fibroblasts, as constructs containing the bacterial chloramphenicol acetyl transferase (CAT) gene driven by a 943 bp pAT133-promoter fragment were induced in these cells by stimulation with PHA/PMA or by serum, respectively. The serum inducible pAT133-promoter lacks consensus serum response elements. However, we could demonstrate that two CArG-like motifs with a single base exchange confer serum inducibility to a reporter construct. Due to their serum responsivness, these elements may serve as a high affinity binding sites for the recently described human serum response factor-related proteins.