HIC1 interacts with FOXP3 multi protein complex: a novel mechanism to regulate human regulatory T cell differentiation and function

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. Highlights Systematic characterization of HIC1 interactome in regulatory T cells by Affinity Purification-Mass Spectrometry HIC1 binds to the RUNX1 promoter and regulates its expression HIC1-a part of FOXP3-RUNX1-CBFB transcriptional complex Graphical abstract