title: Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells.
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-gamma (IFN-gamma). 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-gamma/STAT1 pathway, but also cell-intrinsic transcriptional positive feedback loop between T-bet and OC2 could be involved in Th1 development.
authors.affiliation: Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Furuno
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Hamano
authors.forename: K
authors.initials: K
authors.lastname: Fukuyama
authors.forename: M
authors.initials: M
authors.lastname: Sonoda
authors.forename: T
authors.initials: T
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D018899:CpG Islands / Q000235:genetics; D017930:Genes, Reporter; D006388:Hemagglutinins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D049410:Luciferases, Renilla / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D000098815:T-bet Transcription Factor
chemical_list: D006388:Hemagglutinins; D018398:Homeodomain Proteins; C117354:ONECUT2 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D049410:Luciferases, Renilla