Transcriptional activation by the Werner syndrome gene product in yeast

Werner syndrome (WS) is characterized by the premature occurrence of many a ge-related features. Before the cloning of the gene for WS (WRN), several r eports suggested that transcriptional defects of genes may relate to the me chanisms of the occurrence of WS and natural aging. Because WRN, which enco des a helicase (WRN-H), has been cloned, we are attempting to clarify the m echanism of the transcriptional abnormalities found in WS cells, using WRN and WRN-H. In this article, we studied transcriptional activation of a prom oter by WRN-H in a yeast assay system as a first step. The results showed t hat WRN-H functions as a transcriptional activator in the system. Furthermo re, we performed additional transcriptional assays using various parts of W RN to define the critical region of WRN-H for transcriptional activation in yeast. The results revealed the critical region for the activation most li kely mapped to the region of 315 to 403 aa. The region of 404 to 1309 aa ma y also effect activation in the presence of the critical region. The two re gions contain an acidic domain, and the region of 404 to 1309 aa also conta ins a helicase domain. If this transcriptional activation by WRN-H occurs a lso in human cells in vivo, direct activation of the promoters by WRN-H cou ld explain the results of somatic cell hybrid studies as well as the overex pressed genes detected in WS cells. However, our results should be interpre ted with caution, because thus far, the transcriptional activation by WRN-H were only demonstrated using one promoter in a yeast system. (C) 1998 Else vier Science Inc.