ROLE OF A SPECIFIC NANOG SUPER-ENHANCER ERNA IN EPIGENETIC REMODELING AND ENHANCER-PROMOTER INTERACTION

During last years, the role of enhancer RNAs has been in part explored; however, it’s still not clear the exact role these transcripts carry out concerning gene regulation. In this work, the role of eRNAs transcribed from the region 5kb upper the TSS of Nanog gene in mESCs has been investigated. In particular, a specific eRNA transcript, here defined as antisense eRNA, resulted actively involved in the maintenance of Nanog gene in an active epigenetic state. After the antisense eRNA silencing, Nanog was turned-off and the cell underwent differentiation. This process was achieved through the involvement of the three layers of epigenetic regulation: the hypermethylation of the Nanog promoter and the SE region; the chromatin switch between activation and repression markers; the disruption of the SE-promoter loop responsible of the Nanog gene activation in stemness conditions. Thus, results suggested that the expression of the antisense eRNA has a key role in preserving the pluripotency in mESCs. Futhermore, preliminary experiments were performed on human cancer stem cells models to investigate the presence of eRNAs in a putative enhancer region 3kb upper the NANOG TSS.