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Progenitors are early lineage cells that proliferate before the onset of terminal differentiation. Although widespread, the epigenetic mechanisms that control the progenitor state and the onset of differentiation remain elusive. By studying  Drosophila  ovarian follicle cell progenitors, we identified  lysine-specific demethylase 1  ( lsd1 ) and  CoRest  as differentiation regulators using a GAL4∷GFP variegation assay. The follicle cell progenitors in  lsd1  or  CoRest  heterozygotes prematurely lose epigenetic plasticity, undergo the Notch-dependent mitotic-endocycle transition, and stop dividing before a normal number of follicle cells can be produced. Simultaneously reducing the dosage of the histone H3K4 methyltransferase  Trithorax  reverses these effects, suggesting that an Lsd1/CoRest complex times progenitor differentiation by controlling the stability of H3K4 methylation levels. Individual cells or small clones initially respond to Notch; hence, a critical level of epigenetic stabilization is acquired cell-autonomously and initiates differentiation by making progenitors responsive to pre-existing external signals.

genes and development

The progenitor state is maintained by <i>lysine-specific demethylase 1</i>-mediated epigenetic plasticity during <i>Drosophila</i> follicle cell development

The progenitor state is maintained by lysine-specific demethylase 1-mediated epigenetic plasticity during Drosophila follicle cell development