A1 Refereed original research article in a scientific journal

HIC1 interacts with FOXP3 multi protein complex: Novel pleiotropic mechanisms to regulate human regulatory T cell differentiation and function




AuthorsAndrabi SBA, Batkulwar K, Bhosale SD, Moulder R, Khan MH, Buchacher T, Khan MM, Arnkil I, Rasool O, Marson A, Kalim UU, Lahesmaa R

Publication year2023

JournalImmunology Letters

Journal name in sourceImmunology letters

Journal acronymImmunol Lett

Volume263

First page 123

Last page132

ISSN0165-2478

eISSN1879-0542

DOIhttps://doi.org/10.1016/j.imlet.2023.09.001

Web address https://doi.org/10.1016/j.imlet.2023.09.001

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/181811045


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.

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