Mechanismen der transkriptionellen Regulation durch c-Myc

The c-myc proto-oncogene plays a crucial role in the development of numerous human tumors. To understand how Myc is acting in tumorigenesis, knowledge of interacting proteins and mechanisms is very important. c-myc encodes an evolutionary conserved transcription factor (Myc) that can both activate and repress transcription. There are different and in part poorly understood mechanisms underlying these functions. In the present work, transcriptional mechanisms of Myc and cofactor interactions were investigated at genomic Myc-binding sites of an activated gene (nucleolin) and a repressed gene (c/EBPα). It was shown that MB2-dependent cofactors are recruited to both target genes. In addition Myc-induced histone H4-acetylation as well as serine 5 phosphorylation of the RNAPII complex could be detected on both target genes. The cofactor p300 and the mediator complex instead were recruited only to the Myc-activated gene. Using in vitro- and in vivo-interaction assays, Med24 was identified as a Myc-interacting subunit of the mediator complex. siRNA-based depletion of Med24 in HeLa cells could demonstrate the importance of Med24 for the transactivation function of Myc.