Abstract：
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.
摘要：
转录抑制因子,癌症中的高甲基化1（HIC1）参与一系列重要的生物学过程，比如肿瘤抑制，免疫抑制，胚胎发育和表观遗传基因调控。除此之外，我们先前证明了HIC1对调节性T（Treg）细胞的功能和发育有重要贡献。然而,它调节这些过程的机制并不明显。为了解决这个问题，我们使用亲和纯化质谱来表征人Treg细胞中的HIC1相互作用组。总共确定了61个高置信度的相互作用者，其中IKZF3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，该复合物调节Treg标签基因，从而提高了我们对Treg细胞早期分化过程中HIC1功能的理解。
