Regulation of notch signaling by a chromatin modeling protein Hat-trick

Notch signaling plays pleiotropic role in astounding variety of cellular processes including cell fate determination, differentiation, proliferation and apoptosis. The increasingly complex regulatory mechanisms of Notch signaling account for the multitude of functions exhibited by Notch during development. We identified Hat-trick (Htk), a DNA binding protein, as an interacting partner of Notch-ICD in a yeast two-hybrid screen and their physical interaction was further validated by co-immunoprecipitation experiments. htk genetically interacts with Notch pathway components in trans-heterozygous combinations. Loss of htk function in htk mutant somatic clones showed down-regulation of Notch targets, whereas over-expression of htk caused ectopic expression of Notch target, without affecting the level of Notch protein. Immunocytochemical analysis has demonstrated that Htk co-localizes with over-expressed Notch-ICD in the same nuclear compartment. We have shown here that Htk cooperates with Notch-ICD and Suppressor of Hairless to form activation complex and binds to the regulatory sequences of Notch downstream targets, Enhancer of Split complex genes to direct their expression. Taken together, our results suggest a novel mode of regulation of Notch signaling by a chromatin modeling protein Htk.