Studies of ATF7IP as a novel interaction partner of c-Myb - epigenetic repressor or co-activator?

Abstract

The c-Myb transcription factor is a key regulator of haematopoiesis. Its activity is regulated by a large network of protein interactions and post-translational modifications. ATF7IP is a transcriptional cofactor previously implicated both as a repressive and activating modulator of other transcription factors, depending on site and context. A recent yeast two-hybrid screening in our lab identified ATF7IP as a putative interaction partner of c-Myb. In this thesis, the interaction between ATF7IP and c-Myb was investigated and validated using GST-pulldown analyses. We found ATF7IP to associate with c-Myb in a SUMO-enhanced manner. Initially we proposed two hypothetical models for the functional consequences of how ATF7IP modulates c-Myb function: The Epigenetic Repressor Model and The Mediator-like Activation Model. Using various reporter gene assays, we found no evidence for the first model, but ATF7IP-induced activation in two different reporter assays. We conclude that ATF7IP acts as a novel c-Myb co- activator, presumably by bridging enhancer-bound c-Myb to the general transcription apparatus, thereby promoting the initiation of c-Myb target gene expression.