The human ETS-2 gene promoter: molecular dissection and nuclease hypersensitivity

The human ETS-2 gene is a homolog of the v-ets oncogene of the E26 virus, coding for a 56 kilodalton nuclear protein. Herein we characterize the ETS-2 gene promoter, using a series of deletion constructs. Analysis of the nucleotide sequences from -3600 bp to +141 bp reveal that the region -159 bp to +141 bp is absolutely essential for maximum promoter activity. This region includes half of the lengthy polypyrimidine (CT) tract of the ETS-2 promoter, one Sp1 binding site and the GC element proximal to the initiation site. This CT tract is able to increase in an orientation independent manner, the transcription from alpha-globin promoter. Several S1 hypersensitive sites are found to be located in this promoter region, using chromatin and supercoiled DNA, in close proximity with cis regulatory elements. Our results indicate that an unusually long (approximately 250 bp) CT tract is necessary for ETS-2 transcription and this tract can also serve as a transcription activator using a heterologous promoter.