Abstract
The Gcm/Glide transcription factor is transiently expressed and required in the Drosophila nervous system. Threshold Gcm/Glide levels control the glial versus neuronal fate choice, and its perdurance triggers excessive gliogenesis, showing that its tight and dynamic regulation ensures the proper balance between neurons and glia. Here, we present a genetic screen for potential gcm/glide interactors and identify genes encoding chromatin factors of the Trithorax and of the Polycomb groups. These proteins maintain the heritable epigenetic state, among others, of HOX genes throughout development, but their regulatory role on transiently expressed genes remains elusive. Here we show that Polycomb negatively affects Gcm/Glide autoregulation, a positive feedback loop that allows timely accumulation of Gcm/Glide threshold levels. Such temporal fine-tuning of gene expression tightly controls gliogenesis. This work performed at the levels of individual cells reveals an undescribed mode of Polycomb action in the modulation of transiently expressed fate determinants and hence in the acquisition of specific cell identity in the nervous system.
Highlights
One of the most challenging issues in biology is to elucidate the mechanisms underlying cell fate determination and maintenance
Polycomb group (PcG) and Trithorax group (TrxG) act by triggering stable chromatin modifications that are ‘‘remembered’’ after cell division and keep gene expression in an OFF or ON state
Recent genome-wide analyses call for additional targets of PcG proteins, but the role of these chromatin factors in dynamic transcriptional states and/or in specific cell fates is difficult to apprehend, mostly because very sensitive readouts are required
Summary
One of the most challenging issues in biology is to elucidate the mechanisms underlying cell fate determination and maintenance. Threshold levels of Gcm are necessary and sufficient to induce gliogenesis and the tight regulation of its expression prevents defective/excessive gliogenesis [7,8,9,10,11]. These features make Gcm an ideal tool to study cell differentiation and plasticity. PcG proteins enter two main conserved complexes called Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2) The latter is formed by four core components including, in flies, Enhancer of zeste (E(z)), and catalyzes the reaction that leads to di- and tri-methylation of H3K27. This epigenetic mark is recognized by Polycomb (Pc), which belongs to the PRC1 complex
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