Notch signaling exerts multiple important functions in various developmental processes, including cell differentiation and cell proliferation, while mis-regulation of this pathway results in a variety of complex diseases, such as cancer and developmental defects. The simplicity of the Notch pathway in Drosophila melanogaster, in combination with the availability of powerful genetics, makes this an attractive model for studying the fundamental mechanisms of how Notch signaling is regulated and how it functions in various cellular contexts. Recently, increasing evidence for epigenetic control of Notch signaling reveals the intimate link between epigenetic regulators and Notch signaling pathway. In this chapter, we summarize the research advances of Notch and CAF-1 in Drosophila development and the epigenetic regulation mechanisms of Notch signaling activity by CAF-1 as well as other epigenetic modification machineries, which enables Notch to orchestrate different biological inputs and outputs in specific cellular contexts.
