Год выпуска: 2012 Автор: Ataaillah Benhaddou and Irwin Davidson Издательство: LAP Lambert Academic Publishing Страниц: 188 ISBN: 9783659187155
Описание
The TEAD family of transcription factors is composed of 4 paralogous genes (TEAD1-4) that regulate developmental processes, including myogenesis, and oncogenesis. In this thesis, we show that shRNA-mediated TEAD4 silencing in C2C12 cells causes differentiation defects characterized by shortened myotubes. We performed chromatin immunoprecipitation (ChIP) experiments coupled with hybridization to DNA microarrays (ChIP-chip) to identify TEAD4 target genes as well as RNA-seq to identify TEAD4 transcriptional regulatory network. TEAD4 occupies the promoters of 929 genes, including those of MyoD1 and Myogenin, and myogenic microRNAs. We show that TEAD4 directly induces expression of Myogenin, CDKN1A and Caveolin 3 to promote C2C12 cells differentiation. RNA-seq identifies a set of genes whose expression is strongly reduced upon TEAD4 knockdown amongst which are muscle structural and regulatory proteins and those required for the unfolded protein response (UPR). Preliminary analysis of TEAD4...
