Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells

K. Furuno, K. Ikeda, S. Hamano, K. Fukuyama, M. Sonoda, T. Hara, T. Sasazuki, K. Yamamoto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

T-box transcription factor, T-bet, has a central role in the differentiation of T-helper (Th) progenitor cells to Th1 or Th2 effector cells, partly by regulating the expression of genes such as interferon-γ (IFN-γ). However, the direct target genes, especially those mediating the transcriptional network initiated by T-bet, are not yet fully understood. By combining chromatin immunoprecipitation from Th1 cells with human cytosine-phosphate-guanine-island array analysis, Onecut 2 (OC2), which encodes a member of the ONECUT class of transcriptional activators, was identified as a direct target gene of T-bet. OC2 is expressed in Th1 but not Th2 cells and reporter assays showed that T-bet transactivates OC2 transcription through putative T-bet half-sites locating -451 to -347 of OC2 promoter region. Moreover, we found that OC2 binds and transactivates human T-bet promoter. These results suggest that not only cell-extrinsic regulation via the IFN-γ/STAT1 pathway, but also cell-intrinsic transcriptional positive feedback loop between T-bet and OC2 could be involved in Th1 development.

Original languageEnglish
Pages (from-to)302-308
Number of pages7
JournalGenes and Immunity
Volume9
Issue number4
DOIs
Publication statusPublished - Jun 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Furuno, K., Ikeda, K., Hamano, S., Fukuyama, K., Sonoda, M., Hara, T., Sasazuki, T., & Yamamoto, K. (2008). Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells. Genes and Immunity, 9(4), 302-308. https://doi.org/10.1038/gene.2008.18