title: Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.
abstract: The diverse functions of Notch signalling imply that it must elicit context-specific programmes of gene expression. With the aim of investigating how Notch drives cells to differentiate, we have used a genome-wide approach to identify direct Notch targets in Drosophila haemocytes (blood cells), where Notch promotes crystal cell differentiation. Many of the identified Notch-regulated enhancers contain Runx and GATA motifs, and we demonstrate that binding of the Runx protein Lozenge (Lz) is required for enhancers to be competent to respond to Notch. Functional studies of targets, such as klumpfuss (ERG/WT1 family) and pebbled/hindsight (RREB1 homologue), show that Notch acts both to prevent the cells adopting alternate cell fates and to promote morphological characteristics associated with crystal cell differentiation. Inappropriate activity of Klumpfuss perturbs the differentiation programme, resulting in melanotic tumours. Thus, by acting as a master regulator, Lz directs Notch to activate selectively a combination of target genes that correctly locks cells into the differentiation programme.
authors: Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. sjb32@cam.ac.uk
authors: Ana
authors: A
authors: Terriente-Felix
authors: Jinghua
authors: J
authors: Li
authors: Stephanie
authors: S
authors: Collins
authors: Amy
authors: A
authors: Mulligan
authors: Ian
authors: I
authors: Reekie
authors: Fred
authors: F
authors: Bernard
authors: Alena
authors: A
authors: Krejci
authors: Sarah
authors: S
authors: Bray
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006434:Hemocytes / Q000378:metabolism / Q000502:physiology*; D008156:Luciferases; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D034622:RNA Interference; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C107732:Klu protein, Drosophila; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; C099964:lz protein, Drosophila; C106513:peb protein, Drosophila; D008156:Luciferases