Classifying the molecular functions of transcription factors beyond activation and repression

Notch signaling is a highly conserved pathway activated by dynamic cellular interactions that initiates a molecular cascade that ultimately drives changes in gene expression. The Notch transcriptional complex (NTC) regulates genes that influence development and homeostasis. In this issue of <i>Genes & Development</i>, Rogers and colleagues (doi:10.1101/gad.352108.124) leverage a rapid Notch activation system combined with molecular genomic profiling to reveal that the NTC regulates the release of paused RNA polymerase to activate direct target genes. They also highlight the role of the SWI/SNF chromatin remodeling complex in establishing and maintaining chromatin accessibility to potentiate the activation of NTC target genes.