PROTEOMIC IDENTIFICATION OF THE TRANSCRIPTION FACTORS IKAROS AND AIOLOS AS NEW MYC INTERACTORS ON CHROMATIN

Myc is a transcription factor that plays a key role in many cellular functions. When deregulated, it becomes a potent oncogene and a hallmark of many human cancers. Although its activity has been proven to strongly depend on many cofactors, we are still far from a comprehensive understanding of Myc’s mechanisms of action in transcriptional control. Moreover, since Myc itself is not easily druggable, targeting its cofactors or downstream effectors may constitute a more promising therapeutic strategy in Myc-driven tumors. Here, we have used the Chromatin Proteomics (ChroP) technology to identify new Myc interactors. Among the list of identified candidates, we have chosen to focus our attention on two lymphocyte specific transcription factors, Ikaros and Aiolos. We validated the interaction of Myc with these factors and started to study its functional meaning. Our working hypothesis is that Myc and Ikaros/Aiolos antagonize each other on chromatin at selected target loci. We were able to identify a subset of genes regulated in opposite manners by Ikaros and Myc, involved mainly in cell cycle regulation, metabolism of lipids and metabolic stress response; the next step will be to study more in depth the mechanisms behind their regulation and their functional significance.