Context-Specific Notch Targets Figure 6. Induction heat maps of Notch1 target genes involved in mesoderm development, intracellular signalling cascade, cell proliferation and cytoskeleton. The identified Notch1 targets were grouped into different Gene Ontology (GO) terms using the DAVID functional annotation analysis tool (http://david.abcc.ncifcrf.gov/). Note that only differentially regulated genes by Notch1 are shown as Log2 transformed values. If no gene symbol was available for the regulated transcript, GenBank accession number was given in parentheses. Significant changes of differentially regulated gene expression according to the criteria outlined in Material and Methods were labeled with a black or white dot for up- and down-regulated genes, respectively. Redundant probe sets for the same gene were removed except when significantly different results were obtained (e.g. Sox9). The complete list of regulated genes is available in the Supplement Table S1. doi:10.1371/journal.pone.0011481.g006 induced by Notch1 signaling (Fig. 4, 7, 8H, 10A). Induction of Id genes was significant also in the presence of CHX (Fig. 4, 7, 8H). Thus, like the lineage specific transcription factors, the Id genes are likely direct Notch1 targets. Id proteins function as dominant negative regulators of other bHLH, Ets or Pax transcription factors, which positively regulate differentiation in many cell lineages [41]. Id proteins, which lack a DNA-binding domain, heterodimerize with other transcription factors, either the ubiquitous E proteins or HLH activators, thereby antagonizing their function. In Drosophila, a strong genetic interaction has been found between emc genes, the Drosophila homologue for the Id proteins, and genes that encode different components of the Notch PLoS ONE | www.plosone.org 9 July 2010 | Volume 5 | Issue 7 | e11481