Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
Institute of Pathology, University of Bonn Medical School, Bonn, Germany.
Int J Cancer. 2020 Mar 15;146(6):1592-1605. doi: 10.1002/ijc.32714. Epub 2019 Nov 1.
Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 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 SOX17 in seminoma-like TCam-2 cells to SOX17 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and noncomposite SOX motifs. SOX17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic cells canonical motifs are rarely bound by SOX17. In sum, only 12% of SOX17-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 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 OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.
胚胎癌（ECs）和精原细胞瘤是睾丸生殖细胞肿瘤。ECs 表达 SOX2，而精原细胞瘤表达 SOX17。在体细胞分化中，SOX17 驱动内胚层细胞命运。然而，精原细胞瘤缺乏内胚层标记物的表达，但表现出多能性的特征。在这里，我们使用染色质免疫沉淀测序来报告和比较精原细胞瘤样 TCam-2 细胞中 SOX17 的结合模式与体细胞中的 SOX17 和 EC 样 2102EP 细胞中的 SOX2。在精原细胞瘤样细胞中，SOX17 检测到典型（SOX2/OCT4）、压缩（SOX17/OCT4）和非复合 SOX 基序。SOX17 调节 TFAP2C、PRDM1 和 PRDM14，从而维持潜在的多能性并抑制体细胞分化。相比之下，在体细胞中，SOX17 很少结合典型基序。总的来说，只有 12%的 SOX17 结合位点在精原细胞瘤样和体细胞中重叠。这表明结合位点选择具有高度的动态性和细胞类型特异性。在精原细胞瘤样细胞中删除 SOX17 导致多能性丧失，表现为 OCT4 蛋白水平降低和碱性磷酸酶活性丧失。此外，我们发现 SOX2 在 EC 样细胞中调节多能性相关基因，很可能通过与 OCT4 合作。总之，SOX17（在精原细胞瘤中）功能上取代了 SOX2（在 EC 中），以维持多能性簇的表达。
