Abstract: A highly conserved 48 bp DNA element was identified present at 26 chromosome ends of Saccharomyces cerevisiae. Each element harbours an ideal or a mutated ATF/CREB site, which is a well-known target sequence for bZip transcription factors. In all cases, the sub-telomeric ATF/CREB site element (SACE) is a direct extension of the respective sub-telomeric coreX element. Eight SACEs are part of very long quasi-identical regions of several kilobases, including a sub-telomeric COS open reading frame. Three of these eight SACEs harbour an ideal ATF/CREB site, four a triple-exchange variant (5'-ATG\underline{{\mathrm{{GTA}}}}TCAT-3'; GTA variant), and one a single exchange variant with a C to G exchange at the left side of the center of symmetry. We analyzed the function of the SACE of the left arm of chromosome VIII in vivo and found its ATF/CREB site to act as UAS/URS of the COS8 promoter, effected by the yeast bZip proteins Sko1p, Aca1p, and Aca2p. Cos8 protein was found in proximity to the nuclear membrane, where it accumulated, especially during cell division. When the ATF/CREB site of the COS8 promoter was exchanged with the GTA variant, the regulation was changed. COS8 was then regulated by Hac1p, a bZip protein known to be involved in the unfolded protein response of S. cerevisiae, indicating, for the first time, a possible functional category for the Cos proteins of S. cerevisiae. (c) 2002 Elsevier Science Ltd.