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Interaction of GATA‐3/T‐bet transcription factors regulates homing receptor expression on Th1/Th2 lymphocytes
Author(s) -
Kannagi Reiji,
Chen GuoYun,
Osada Hirotaka,
SantamariaBabi Luis F
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a285-a
Subject(s) - transcription factor , homing (biology) , gata2 , microbiology and biotechnology , binding site , chemistry , promoter , lymphocyte homing receptor , transcription (linguistics) , t cell , biology , gene , cell adhesion , gene expression , cell , biochemistry , genetics , immune system , ecology , linguistics , philosophy
Here we show that a gene involved in selectin ligand synthesis has binding sites for, and regulated by, T‐bet and GATA‐3, two opposing factors for T‐helper‐1 (Th1) and T‐helper‐2 (Th2) differentiation. Selectin‐dependent cell adhesion mediates homing and inflammatory extravasation of lymphocytes. Th1 cells are known to more preferentially express sialyl Lewis X, the specific carbohydrate ligand for selectins, compared to Th2 cells. The molecular basis for this, however, has not been elucidated to date. The gene for fucosyltransferase VII ( FUT7 ), the rate‐limiting enzyme for sialyl Lewis X synthesis, is a unique example of the human genes in that it has binding sites for both GATA‐3 and T‐bet, and is transcriptionally regulated by a balance of the two interacting transcription factors. T‐bet promotes FUT7 transcription by recruiting CBP/P300, and GATA‐3 represses it by phosphorylation‐dependently recruiting HDAC‐3/‐5, and by competing with CBP/P300 for binding to N‐terminus of T‐bet. T‐bet interfered with the binding of GATA‐3 to its target DNA, and GATA‐3 significantly interfered with the binding of T‐bet to the FUT7 promoter. These results indicate that the GATA‐3/T‐bet transcription factors regulate the cell‐lineage‐specific expression of the lymphocyte homing receptors.