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

Syed Bilal Ahmad Andrabi; Kedar Batkulwar; Santosh D. Bhosale; Robert Moulder; Meraj Hasan Khan; Tanja Buchacher; Mohd Moin Khan; Ilona Arnkil; Omid Rasool; Alexander Marson; Ubaid Ullah Kalim; Riitta Lahesmaa

doi:10.1016/j.imlet.2023.09.001

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

Syed Bilal Ahmad Andrabi
, Kedar Batkulwar
, Santosh D. Bhosale
, Robert Moulder
, Meraj Hasan Khan
, Tanja Buchacher
, Mohd Moin Khan
, Ilona Arnkil
, Omid Rasool
, Alexander Marson
, Ubaid Ullah Kalim
, Riitta Lahesmaa^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

4 Citations (Scopus)

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.

Original language	English
Pages (from-to)	123-132
Number of pages	10
Journal	Immunology Letters
Volume	263
DOIs	https://doi.org/10.1016/j.imlet.2023.09.001
Publication status	Published - Nov 2023
MoE publication type	A1 Journal article-refereed

Funding

RL was supported by the Academy of Finland (AoF) center of Excellence in Molecular Systems Immunology and Physiology Research (2012–2017) grant 250114 ; by the AoF grants 292335 , 294337 , 292482 , 319280 , 329277 , 331793 , 335435 and 31444 ; by grants from the JDRF; the Novo Nordisk Foundation (grant NNF19OC0057218 ); the Sigrid Jusélius Foundation; Jane and Aatos Erkko Foundation and the Finnish Cancer Foundation. Our research is also supported by University of Turku , Åbo Akademi University, Turku Graduate School, InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530). SBAA, was supported by InFLAMES Postdoctoral fellowship Programme, Finnish Cultural Foundation and Maud Kuistila Memorial Foundation. KB was supported by Orion Research Foundation sr and Finnish Cultural Foundation.

Keywords

FOXP3
HIC1
Immunoprecipitation
Interactome
iTreg
RUNX1

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10.1016/j.imlet.2023.09.001

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Andrabi, S. B. A., Batkulwar, K., Bhosale, S. D., Moulder, R., Khan, M. H., Buchacher, T., Khan, M. M., Arnkil, I., Rasool, O., Marson, A., Kalim, U. U., & Lahesmaa, R. (2023). HIC1 interacts with FOXP3 multi protein complex: Novel pleiotropic mechanisms to regulate human regulatory T cell differentiation and function. Immunology Letters, 263, 123-132. https://doi.org/10.1016/j.imlet.2023.09.001

@article{19f0ccc3378e4870a3152352241b05ee,

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

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.",

keywords = "FOXP3, HIC1, Immunoprecipitation, Interactome, iTreg, RUNX1, FOXP3, RUNX1, iTreg, Interactome, Immunoprecipitation, HIC1",

author = "Andrabi, \{Syed Bilal Ahmad\} and Kedar Batkulwar and Bhosale, \{Santosh D.\} and Robert Moulder and Khan, \{Meraj Hasan\} and Tanja Buchacher and Khan, \{Mohd Moin\} and Ilona Arnkil and Omid Rasool and Alexander Marson and Kalim, \{Ubaid Ullah\} and Riitta Lahesmaa",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = nov,

doi = "10.1016/j.imlet.2023.09.001",

language = "English",

volume = "263",

pages = "123--132",

journal = "Immunology Letters",

issn = "0165-2478",

publisher = "Elsevier",

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Andrabi, SBA, Batkulwar, K, Bhosale, SD, Moulder, R, Khan, MH, Buchacher, T, Khan, MM, Arnkil, I, Rasool, O, Marson, A, Kalim, UU & Lahesmaa, R 2023, 'HIC1 interacts with FOXP3 multi protein complex: Novel pleiotropic mechanisms to regulate human regulatory T cell differentiation and function', Immunology Letters, vol. 263, pp. 123-132. https://doi.org/10.1016/j.imlet.2023.09.001

TY - JOUR

T1 - HIC1 interacts with FOXP3 multi protein complex

T2 - Novel pleiotropic mechanisms to regulate human regulatory T cell differentiation and function

AU - Andrabi, Syed Bilal Ahmad

AU - Batkulwar, Kedar

AU - Bhosale, Santosh D.

AU - Moulder, Robert

AU - Khan, Meraj Hasan

AU - Buchacher, Tanja

AU - Khan, Mohd Moin

AU - Arnkil, Ilona

AU - Rasool, Omid

AU - Marson, Alexander

AU - Kalim, Ubaid Ullah

AU - Lahesmaa, Riitta

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - FOXP3

KW - HIC1

KW - Immunoprecipitation

KW - Interactome

KW - iTreg

KW - RUNX1

KW - FOXP3

KW - RUNX1

KW - iTreg

KW - Interactome

KW - Immunoprecipitation

KW - HIC1

UR - https://www.scopus.com/pages/publications/85175147096

U2 - 10.1016/j.imlet.2023.09.001

DO - 10.1016/j.imlet.2023.09.001

M3 - Article

C2 - 37838026

AN - SCOPUS:85175147096

SN - 0165-2478

VL - 263

SP - 123

EP - 132

JO - Immunology Letters

JF - Immunology Letters

ER -

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

Abstract

Funding

Keywords

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