Yin Yang 1 Orchestrates a Metabolic Program Required for Both Neural Crest Development and Melanoma Formation.
Increasing evidence suggests that cancer cells highjack developmental programs for disease initiation and progression. Melanoma arises from melanocytes that originate during development from neural crest stem cells (NCSCs). Here, we identified the transcription factor Yin Yang 1 (Yy1) as an NCSCs regulator. Conditional deletion of Yy1 in NCSCs resulted in stage-dependent hypoplasia of all major neural crest derivatives due to decreased proliferation and increased cell death. Moreover, conditional ablation of one Yy1 allele in a melanoma mouse model prevented tumorigenesis, indicating a particular susceptibility of melanoma cells to reduced Yy1 levels. Combined RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and untargeted metabolomics demonstrated that YY1 governs multiple metabolic pathways and protein synthesis in both NCSCs and melanoma. In addition to directly regulating a metabolic gene set, YY1 can act upstream of MITF/c-MYC as part of a gene regulatory network controlling metabolism. Thus, both NCSC development and melanoma formation depend on an intricate YY1-controlled metabolic program.
['Varum|Sandra|S|', 'Baggiolini|Arianna|A|', 'Zurkirchen|Luis|L|', 'Atak|Zeynep Kalender|ZK|', 'Cantù|Claudio|C|', 'Marzorati|Elisa|E|', 'Bossart|Raphaël|R|', 'Wouters|Jasper|J|', 'Häusel|Jessica|J|', 'Tuncer|Eylül|E|', 'Zingg|Daniel|D|', 'Veen|Dominiek|D|', 'John|Nessy|N|', 'Balz|Marcel|M|', 'Levesque|Mitchell P|MP|', 'Basler|Konrad|K|', 'Aerts|Stein|S|', 'Zamboni|Nicola|N|', 'Dummer|Reinhard|R|', 'Sommer|Lukas|L|']
D000818:Animals D045744:Cell Line, Tumor D006801:Humans D008545:Melanoma D051379:Mice D018345:Mice, Knockout D008822:Mice, Transgenic D009432:Neural Crest D058953:Neural Stem Cells D050986:YY1 Transcription Factor
metabolism neural crest development melanoma YY1 protein synthesis tumor initiation