Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate

摘要

Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOXl 7 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use chromatin immunoprecipitation sequencing to report and compare the binding pattern of SOXl 7 in seminoma-like TCam-2 cells to SOXl 7 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOXl 7 was detected at canonical (SOX2/OCT4), compressed (SOXl 7/0CT4) and noncomposite SOX motifs. S0X17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic celts canonical motifs are rarely bound by SOXl7. In sum, only 12% of SOXl 7-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is high ly dynamic and cell type specific. Deletion of SOXl 7 in seminoma-like ceils resulted in loss of pluripotency, marked by a reduction of 0CT4 protein level and loss of alkaline phosphatase activity. Furthermore, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, most likely by partnering with 0CT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.