DOI: 10.1101/488387Dec 6, 2018Paper

The coordination of terminal differentiation and cell cycle exit is mediated through the regulation of chromatin accessibility

BioRxiv : the Preprint Server for Biology
Yiqin MaLaura Buttitta

Abstract

During terminal differentiation most cells will exit the cell cycle and enter into a prolonged or permanent G0. Cell cycle exit is usually initiated through the repression of cell cycle gene expression by formation of a transcriptional repressor complex called DREAM. However when DREAM repressive function is compromised during terminal differentiation, additional unknown mechanisms act to stably repress cycling and ensure robust cell cycle exit. Here we provide evidence that developmentally programmed, temporal changes in chromatin accessibility at a subset of critical cell cycle genes acts to enforce cell cycle exit during terminal differentiation in the Drosophila melanogaster wing. We show that during terminal differentiation, chromatin closes at a set of pupal wing enhancers for the key rate-limiting cell cycle regulators cycE, e2f1 and stg. This closing coincides with wing cells entering a robust postmitotic state that is strongly refractory to cell cycle re-activation. When cell cycle exit is genetically disrupted, chromatin accessibility at cell cycle genes remains largely unaffected and the closing of enhancers at cycE, e2f1 and stg proceeds independent of the cell cycling status. Instead, disruption of cell cycle exit ...Continue Reading

Related Concepts

Cell Cycle
Cell Differentiation Process
Chromatin
Dreams
Drosophila melanogaster
Enzyme Repression
Gene Expression
Hormones
Biological Metamorphosis
Transcription, Genetic

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