tailieunhanh - Báo cáo khoa học: Novel target genes of the Wnt pathway and statistical insights into Wnt target promoter regulation

The Wnt pathway controls biological processes via the regulation of target gene expression. The expression of direct Wnt target genes, D1 and MYC, is activated by the transcription factor TCF, which binds to specific sequence motifs in the promoter. Indirect target genes are regulated via transcription regulators, which are targets of the Wnt pathway. | iFEBS Journal Novel target genes of the Wnt pathway and statistical insights into Wnt target promoter regulation Slava Ziegler1 Sonja Rohrs1 Lara Tickenbrock2 Tarik Moroy3 Ludger Klein-Hitpass3 Ingrid R. Vetter1 and Oliver Muller1 1 Max-Planck-Institut fur molekulare Physiologie Dortmund Germany 2 Interdisziplinares Zentrum fur Klinische Forschung Universitatsklinikum Munster Munster Germany 3 Institut fur Zellbiologie Tumorforschung Universitatsklinikum Essen Germany Keywords microarray analysis statisticalanalysis of transcription factor motifs transcription factor binding site Wnt pathway Wnt target gene Correspondence O. Muller Max-Planck-Institut fur molekulare Physiologie Otto-Hahn-StraBe 11 44227 Dortmund Germany Fax 49 231 133 2199 Tel 49 231 133 2158 E-mail . Received 15 December 2004 revised 19 January 2005 accepted 24 January 2005 doi The Wnt pathway controls biological processes via the regulation of target gene expression. The expression of direct Wnt target genes . cyclin D1 and MYC is activated by the transcription factor TCF which binds to specific sequence motifs in the promoter. Indirect target genes are regulated via transcription regulators which are targets of the Wnt pathway. As an example MYC regulates the MYC interacting zinc finger protein-1 MIZ-1 which is able to inhibit the expression of the indirect target p21WAF1. We intended to identify new Wnt target genes and to get a deeper insight into the regulatory mechanisms of Wnt target gene expression. For this we analyzed the differential expression pattern of Wnt-1 activated cells by microarray analysis. We identified 43 sequences including eight expressed sequence tags ESTs which showed increased transcript levels and 104 sequences including 19 ESTs with decreased RNA levels. Northern blot and real-time quantitative PCR analysis of the differential expression levels of 15 genes confirmed the differential expression .