A GATA/RUNX cis-regulatory module couples Drosophila blood cell commitment and differentiation into crystal cells.
Members of the RUNX and GATA transcription factor families play critical roles during hematopoiesis from Drosophila to mammals. In Drosophila, the formation of the crystal cell hematopoietic lineage depends on the continuous expression of the lineage-specific RUNX factor Lozenge (Lz) and on its interaction with the GATA factor Serpent (Srp). Crystal cells are the main source of prophenoloxidases (proPOs), the enzymes required for melanization. By analyzing the promoter regions of several insect proPOs, we identify a conserved GATA/RUNX cis-regulatory module that ensures the crystal cell-specific expression of the three Drosophila melanogaster proPO. We demonstrate that activation of this module requires the direct binding of both Srp and Lz. Interestingly, a similar GATA/RUNX signature is over-represented in crystal cell differentiation markers, allowing us to identify new Srp/Lz target genes by genome-wide screening of Drosophila promoter regions. Finally, we show that the expression of lz in the crystal cells also relies on Srp/Lz-mediated activation via a similar module, indicating that crystal cell fate choice maintenance and activation of the differentiation program are coupled. Based on our observations, we propose that this GATA/RUNX cis-regulatory module may be reiteratively used during hematopoietic development through evolution.
Ferjoux
Géraldine
G
Centre de Biologie du Développement, UMR 5547, CNRS/Université Paul Sabatier Toulouse III, 118 route de Narbonne, 31062 Toulouse, France.
Augé
Benoit
B
Boyer
Karène
K
Haenlin
Marc
M
Waltzer
Lucas
L
D000818:Animals; D004156:Catechol Oxidase / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D017124:Conserved Sequence; D050657:Core Binding Factor alpha Subunits / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000201:enzymology / Q000254:growth & development; D004792:Enzyme Precursors / Q000235:genetics; D050980:GATA Transcription Factors / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006434:Hemocytes / Q000166:cytology*; D007814:Larva / Q000166:cytology / Q000254:growth & development; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology
D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D004792:Enzyme Precursors; D050980:GATA Transcription Factors; D014157:Transcription Factors; C099964:lz protein, Drosophila; C103965:srp protein, Drosophila; C038451:pro-phenoloxidase; D004156:Catechol Oxidase