Regulation of the expression of HMG1, a co-activator of the estrogen receptor

HMG1 is a protein of high clinical significance. Besides shielding of DNA a dducts against repair enzymes making cells mole sensitive to cisplatin ther apy, if is also a co-modulator of the activity of steroid hormone-regulated genes. Although HMG1 is regulated by various factors, including steroid ho rmone estrogen, nothing M,ns known about regulatory sequences. Also the seq uence of parts of HMG1 including its promoter remains still unknown. We hav e completed the genomic organization of human HMG1 and characterized its re gulatory region by luciferase assay for promoter activity. Insights into th e regulation of HMG1 expression are given by the promoter analysis showing a strong functional promoter; enhancing and negative regulatory regions tog ether with a CpG island in intron I and several transcription factor bindin g sites. Furthermore, the finding of two estrogen responsive elements withi n intron 1 is relevant as they indicate a db ect mechanism of HMG1 up-regul ation by estrogen making the presence of an estrogen receptor a significant marker for a combined treatment of special tumor types with estrogen and t he anticancer drugs cisplatin or carboplatin.