TY - JOUR
T1 - Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells
AU - Furuno, K.
AU - Ikeda, K.
AU - Hamano, S.
AU - Fukuyama, K.
AU - Sonoda, M.
AU - Hara, T.
AU - Sasazuki, T.
AU - Yamamoto, K.
N1 - Funding Information:
We thank T Tanaka, T Akinaga, M Goto and M Ohnish for technical help. This work was supported by a Grant-in-Aid for Scientific Research in the priority area of Genome Biology, and by a grant from the 21st Center of Excellence Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=44849133856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44849133856&partnerID=8YFLogxK
U2 - 10.1038/gene.2008.18
DO - 10.1038/gene.2008.18
M3 - Article
C2 - 18418398
AN - SCOPUS:44849133856
VL - 9
SP - 302
EP - 308
JO - Genes and Immunity
JF - Genes and Immunity
SN - 1466-4879
IS - 4
ER -