Journal
DEVELOPMENT
Volume 140, Issue 4, Pages 926-937Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.086785
Keywords
Lozenge/Runx; Notch; Chromatin immunoprecipitation; Haemocyte; Drosophila
Categories
Funding
- Medical Research Council [G0800034]
- Biotechnology and Biological Sciences Research Council
- China Scholarship Council
- Genetics Society summer studentship
- Grantova agentura Ceske republiky [P305/11/0126]
- MRC [G0500926, G0800034] Funding Source: UKRI
- Medical Research Council [G0500926, G0800034] Funding Source: researchfish
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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.
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