National Academy of Sciences, Proceedings of the National Academy of Sciences, 12(114), 2017
Full text: Download
Significance The spatial organization of chromatin within the nucleus regulates genomic functions including DNA repair, transcription, and replication. For example, replication origins cluster prior to initiating replication, likely to aggregate the many necessary factors, but the mechanism is poorly understood. We recently discovered yeast “Forkhead Box” (Fox) DNA binding proteins, Forkhead 1 (Fkh1) and Forkhead 2 (Fkh2), as required for this origin clustering and regulation of initiation timing. This study reveals that Fkh1 and Fkh2 share a structural motif that allows dimerization to bring distal DNA binding sites into close proximity. Mutation that disrupts dimerization ablates origin clustering and deregulates origin activation, suggesting causality between origin clustering and initiation control. We propose that Fkh1 and Fkh2 and related Fox proteins in metazoans establish chromatin architecture.