2006年11月
Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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- 巻
- 103
- 号
- 45
- 開始ページ
- 16894
- 終了ページ
- 16899
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1073/pnas.0607926103
- 出版者・発行元
- NATL ACAD SCIENCES
Selectin-dependent cell adhesion mediates inflammatory extravasation and routine homing of lymphocytes. Most resting peripheral T lymphocytes lack expression of sialyl Lewis X, the carbohydrate ligand for selectins, and are induced to strongly express it upon activation. T helper 1 (Th1) cells are known to more preferentially express sialyl Lewis X as compared with T helper 2 (Th2) cells upon activation. The molecular basis for this preferential expression, however, has not been elucidated to date. Here we show that the gene for fucosyltransferase VII (FUT7), the rate-limiting enzyme for sialyl Lewis X synthesis, is a unique example of the human genes with binding sites for both GATA-3 and T-bet, two opposing factors for Th1 and Th2 development, and is regulated transcriptionally by a balance of the two interacting transcription factors. T-bet promotes and GATA-3 represses FUT7 transcription. bur results indicated that T-bet interferes with the binding of GATA-3 to its target DNA, and also that GATA-3 significantly interferes with the binding of T-bet to the FUT7 promoter. T-bet has a binding ability to GATA-3, CBP/P300, and Sp1 to form a transcription factor complex, and GATA-3 regulates FUT7 transcription by phosphorylation-dependently recruiting histone deacetylase (HDAC)-3/HDAC-5 and by competing with CBP/P300 in binding to the N terminus of T-bet. Suppression of GATA-3 activity by dominant-negative GATA-3 or repressor of GATA (ROG) was necessary to attain a maximum expression of FUT7 and sialyl Lewis X in human T lymphoid cells. These results indicate that the GATA-3/T-bet transcription factor complex regulates the cell-lineage-specific expression of the lymphocyte homing receptors.
- リンク情報
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- DOI
- https://doi.org/10.1073/pnas.0607926103
- CiNii Articles
- http://ci.nii.ac.jp/naid/10024357103
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/17075044
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000241969500049&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1073/pnas.0607926103
- ISSN : 0027-8424
- CiNii Articles ID : 10024357103
- PubMed ID : 17075044
- Web of Science ID : WOS:000241969500049