| Recent work has shown that most RNA does not encode for protein. The function of these non-coding RNAs is largely unknown, but evidence suggests that they are involved in the regulation of gene transcription. This proposal aims at the identification of specific non-coding RNAs and their binding sites, involved in the regulation of gene transcription. Gene transcription depends on local chromatin status and transcription factors bound at the promoter region. However, initiation of transcription is predominantly controlled by long-range genetic interactions between promoter and enhancer regions. Repressed chromatin at a promoter region can obstruct these long range interactions. Very recently it has been shown that AGO1 is a critical component in mediating repressed chromatin, which is recruited by non-coding RNA. I will use AGO1 to identify non-coding RNAs and local DNA regions to reveal both the identity of the non-coding RNAs and the location of AGO1-ncRNA interactions along the genome. The identity of AGO1-RNA interactions will provide new insights in previously unknown roles of RNA in (long-range) transcriptional regulation. Recruitment of AGO1 by non-coding RNAs may be a mechanism that leads to aberrant gene transcription found in stem cells and pathophysiological conditions such as cancer. |
