Fat cadherin cleavage releases a transcriptionally active nuclear fragment to regulate target gene expression

Working at the apical-junctional plasma membrane, the intracellular domain of the Ft protein, FtICD, binds to and regulates components of the Hippo and PCP pathways. Unexpectedly, we find that a fragment of the FtICD is present in the nucleus in cultured cells as well as in embryonic and larval tissues, and we identify nuclear localization and nuclear export signals in FtICD required for this localization.

We show that membrane-bound FtICD is cleaved and enters nuclei in vivo. Using endogenously tagged Ft as well as overexpressed FtICD, we conducted ChIP-seq experiments and identified putative Ft targets, including genes involved in signaling pathways, chromatin organization, pattern formation, and neural development. RNAseq demonstrates that some of these genes are dysregulated in ft mutants.