{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:23:06Z","timestamp":1762100586231},"reference-count":39,"publisher":"Proceedings of the National Academy of Sciences","issue":"45","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,11,7]]},"abstract":"<jats:p>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 (<jats:italic>FUT7<\/jats:italic>), 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<jats:italic>FUT7<\/jats:italic>transcription. Our 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<jats:italic>FUT7<\/jats:italic>promoter. T-bet has a binding ability to GATA-3, CBP\/P300, and Sp1 to form a transcription factor complex, and GATA-3 regulates<jats:italic>FUT7<\/jats:italic>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<jats:italic>FUT7<\/jats:italic>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.<\/jats:p>","DOI":"10.1073\/pnas.0607926103","type":"journal-article","created":{"date-parts":[[2006,10,31]],"date-time":"2006-10-31T01:48:28Z","timestamp":1162259308000},"page":"16894-16899","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":80,"title":["Interaction of GATA-3\/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1\/Th2 lymphocytes"],"prefix":"10.1073","volume":"103","author":[{"given":"Guo-Yun","family":"Chen","sequence":"first","affiliation":[{"name":"Departments of *Molecular Pathology and"},{"name":"Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan; and"}]},{"given":"Hirotaka","family":"Osada","sequence":"additional","affiliation":[{"name":"Molecular Oncology, Aichi Cancer Center, Nagoya 464-8681, Japan;"}]},{"given":"Luis F.","family":"Santamaria-Babi","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital del Mar, Institut Municipal d'Assistencia Sanitaria, Barcelona 08003, Spain"}]},{"given":"Reiji","family":"Kannagi","sequence":"additional","affiliation":[{"name":"Departments of *Molecular Pathology and"},{"name":"Core Research for Evolutionary Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan; 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