Investigating the role of KDM2A in CpG island function and transcription regulation. (360G-Wellcome-102349_Z_13_Z)

KDM2A is recruited to CpG islands (CGIs) throughout the genome. CGIs are regions of non-methylated DNA, and are associated with the majority of mammalian gene promoters. Here it has been proposed that KDM2A catalyses the removal of dimethyl histone H3 lysine 36, an abundant modification that can inhibit transcription initiation. Localised removal of this inhibitory mark byKDM2A may contribute to the generation of a promoter-associated transcriptionally permissive chromatin landscape. I aim to directly examine the role that KDM2A plays in regulating CpG island associated chromatin architecture and gene expression. To achieve this, initially a simple transgene reporter system will be used to determine the effect that KDM2A recruitment has on gene expression and to determine which regions of the protein to contribute this activity. Transcription regulation by KDM2A will next be investigated genome-wide, using KDM2A knockout mouse embryonic stem cells. Transcription and chromatin architecture in the wild-type and KDM2A knockout cells will then be examined in detail. This will