Genome-wide mapping of histone modifications and transcription factor occupancy in Fbw7 mutant cells [CUTandRUN]

Fbw7 is one of the most highly mutated tumor suppressor genes in human cancers. Several Fbw7 mutation types have been found in cancers (e.g. Fbw7Arg/+, other missense mutations and Fbw7-/-). Fbw7Arg/+ missense mutation is the most commonly observed mutation type, however the tumorigenic mechanisms led by Fbw7Arg/+ are as of yet poorly understood. Fbw7 targets almost thirty proteins to degradation, out of many are transcription factors. We performed an integrative study to understand global transcriptional regulation by Fbw7. We investigated the deregulation of two well-studied oncogenic Fbw7 substrates: cMyc and cJun in wild-type and Fbw7 mutant colorectal cancer cell lines and neural stem cells. Our study revealed context-specific transcriptional regulation by Fbw7. We used Cleavage Under Targets and Release Using Nuclease (CUTandRUN), a chromatin profiling strategy to map the genome-wide histone modifications and transcription factors in wild-type and Fbw7 mutant cells (Fbw7-/- and Fbw7R505C/+). Three replicates per cell condition and an IgG negative control were included for each experiment.