Andrabi Syed Bilal Ahmad, Batkulwar Kedar, Bhosale Santosh D, Moulder Robert, Khan Meraj Hasan, Buchacher Tanja, Khan Mohd Moin, Arnkil Ilona, Rasool Omid, Marson Alexander, Kalim Ubaid Ullah, Lahesmaa Riitta
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland; InFLAMES Research Flagship Center, University of Turku.
Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland; Precision Biomarker Laboratories, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Immunol Lett. 2023 Nov;263:123-132. doi: 10.1016/j.imlet.2023.09.001. Epub 2023 Oct 12.
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.
癌症中高甲基化的转录抑制因子1（HIC1）参与一系列重要的生物学过程，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）细胞的功能和发育有重大贡献。然而，其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Treg细胞中的HIC1相互作用组。共鉴定出61个高可信度的相互作用蛋白，包括IKZF3，它是Treg细胞发育中的关键转录因子。与这些相互作用蛋白相关的生物学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特征基因，从而增进了我们对HIC1在早期Treg细胞分化过程中功能的理解。
