The Notch signalling pathway regulates a variety of cellular events, including differentiation, proliferation and apoptosis. Compared with many other signalling events, this pathway is relatively simple; however, the context-dependent activity of numerous proteins that can influence Notch signalling increases its complexity and specificity. Here, Elena Domanitskaya and Trudi Schüpbach (p. 399) identify the transcriptional cofactor CoREST as a new positive regulator that mediates epigenetic regulation through the Notch signalling pathway in Drosophila. Ovarian follicle cells lacking CoREST show defects in the Notch-dependent mitotic-to-endocycle switch and in the expression of Notch target genes. The authors find, that CoREST acts downstream of Notch proteolytic cleavage, but upstream of the Notch target gene Hindsight, which regulates the mitotic-to-endocycle switch. Furthermore, CoREST antagonises the activity of components of the Notch repressor complex, such as Hairless, C-terminal Binding Protein and Groucho, and the absence of CoREST results in increased levels of H3K27 trimethylation and H4K16 acetylation. Taken together, these results highlight that CoREST is a positive regulator of Notch signalling in Drosophila.
CoREST turns signal up a Notch
CoREST turns signal up a Notch. J Cell Sci 15 January 2012; 125 (2): e204. doi:
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