Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data

Stefano Magni, Rucha Sawlekar, Christophe M. Capelle, Vera Tslaf, Alexandre Baron, Ni Zeng, Laurent Mombaerts, Zuogong Yue, Ye Yuan, Feng Q. Hefeng, Jorge Gonçalves*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1 Citation (Scopus)

Abstract

The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.

Original languageEnglish
Pages (from-to)59
Number of pages1
Journalnpj Systems Biology and Applications
Volume10
Issue number1
DOIs
Publication statusPublished - 29 May 2024

Keywords

  • Humans
  • Forkhead Transcription Factors/genetics
  • T-Lymphocytes, Regulatory/immunology
  • Transcriptome/genetics
  • Computational Biology/methods
  • Gene Expression Regulation/genetics
  • Gene Expression Profiling/methods
  • Genes, Regulator/genetics

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