Transcriptional repressor, hypermethylated in cancer 1 (HIC1) participates in a range of important biological processes, such as tumor repression, immune suppression, embryonic development and epigenetic gene regulation. Further to these, we previously demonstrated that HIC1 provides a significant contribution to the function and development of regulatory T (Treg) cells. However, the mechanism by which it regulates these processes was not apparent. To address this question, we used affinity-purification mass spectrometry to characterize the HIC1 interactome in human Treg cells. Altogether 61 high-confidence interactors were identified, including IKZF3, which is a key transcription factor in the development of Treg cells. The biological processes associated with these interacting proteins include protein transport, mRNA processing, non-coding (ncRNA) transcription and RNA metabolism. The results revealed that HIC1 is part of a FOXP3-RUNX1-CBFB protein complex that regulates Treg signature genes thus improving our understanding of HIC1 function during early Treg cell differentiation.

癌症高甲基化转录抑制因子 1 (HIC1) 参与一系列重要的生物过程，例如肿瘤抑制、免疫抑制、胚胎发育和表观遗传基因调控。除此之外，我们之前证明 HIC1 对调节性 T (Treg) 细胞的功能和发育做出了重大贡献。然而，它调节这些过程的机制尚不清楚。为了解决这个问题，我们使用亲和纯化质谱法来表征人类 Treg 细胞中的 HIC1 相互作用组。总共鉴定出了 61 个高可信度相互作用因子，其中包括 IKZF3，它是 Treg 细胞发育中的关键转录因子。与这些相互作用的蛋白质相关的生物过程包括蛋白质转运、mRNA 加工、非编码 (ncRNA) 转录和 RNA 代谢。结果表明，HIC1 是 FOXP3-RUNX1-CBFB 蛋白复合物的一部分，可调节 Treg 特征基因，从而提高我们对早期 Treg 细胞分化过程中 HIC1 功能的理解。