Smad1, β-catenin and Tcf4 associate in a molecular complex with the Myc promoter in dysplastic renal tissue and cooperate to control Myc transcription

• DOI: 10.1242/dev.01573
• Publication Date: 2004-12-03T01:18:10Z
• Authors: Ming Chang Hu; Norman D. Rosenblum
• Keywords: TCF4; Transcription; Beta-catenin; Chromatin immunoprecipitation

Renal dysplasia, the major cause of childhood renal failure in humans, arises from perturbed morphogenesis and molecular signaling during embryogenesis. Recently, we discovered induction crosstalk between Smad1 beta-catenin TgAlk3QD mouse model medullary cystic dysplasia. Our finding that Myc, a Smad transcriptional target effector epithelial dedifferentiation, is misexpressed dedifferentiated tubules provided basis for investigating coordinate control by disease. Here, report enhanced interactions complex consisting Smad1, Tcf4 adjacent Tcf- Smad-binding regions located within Myc promoter dysplastic tissue, Bmp-dependent cooperative transcription Tcf4. Analysis nuclear extracts derived wild-type tissue revealed increased levels Smad1/beta-catenin complexes, de novo formation chromatin-associated Tcf4/Smad1 complexes tissues. 476 nucleotide segment 1490 genomic region upstream start site demonstrated consensus binding associations with oligo-duplexes encode elements only In collecting duct cells express luciferase under region, Bmp2-dependent stimulation was dependent on contributions each Tcf4, Smad1. These results provide novel insights into mechanisms which interacting pathways genesis