A novel transcriptional cascade is involved in Fzr-mediated endoreplication

摘要: Endoreplication, known as endocycle, is a variant of the cell cycle that differs from mitosis and occurs in specific tissues different organisms. Endoreplicating cells generally undergo multiple rounds genome replication without chromosome segregation. Previous studies demonstrated Drosophila fizzy-related protein (Fzr) its mammalian homolog Cdh1 function key regulators endoreplication entrance by activating anaphase-promoting complex/cyclosome to initiate ubiquitination subsequent degradation factors such Cyclin B (CycB). However, molecular mechanism underlying Fzr-mediated not completely understood. In this study, we transcription factor Myc acts downstream Fzr during salivary gland. Mechanistically, interacts with chromatin-associated histone H2B enhance promoter promotes transcription. addition negatively regulating CycB transcription, Fzr-ubiquitinated (H2Bub)-Myc signaling cascade also positively regulates MCM6 gene involved DNA directly binding motifs within their promoters. We further found Fzr-H2Bub-Myc progression conserved between insects cells. Altogether, our work uncovers novel transcriptional endoreplication.