CITED1 is a novel binding partner of MITF that influences the MITF-directed transcriptional profile in melanoma
We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.