GATA-3 is a master regulator of T helper type 2 (T(H)2) differentiation. However, the molecular basis of GATA-3-mediated T(H)2 lineage commitment is poorly understood. Here we identify the DNase I-hypersensitive site 2 (HS2) element located in the second intron of the interleukin 4 locus (Il4) as a critical enhancer strictly controlled by GATA-3 binding. Mice lacking HS2 showed substantial impairment in their asthmatic responses and their production of IL-4 but not of other T(H)2 cytokines. Overexpression of Gata3 in HS2-deficient T cells failed to restore Il4 expression. HS2 deletion impaired the trimethylation of histone H3 at Lys4 and acetylation of histone H3 at Lys9 and Lys14 in the Il4 locus. Our results indicate that HS2 is the target of GATA-3 in regulating chromosomal modification of the Il4 locus and is independent of the Il5 and Il13 loci.
We found previously that the ingestion of margarine containing medium-chain triacylglycerols (MCT) resulted in a significant increase in postprandial thermogenesis when compared with long-chain triacylglycerols (LCT). Diets that included margarine containing MCT and LCT were compared for 12 weeks in 73 subjects to investigate the effects on body weight, body fat, areas of subcutaneous and visceral fat, serum total cholesterols, triglycerides, lipoproteins, plasma glucose, serum insulin, total ketone bodies, and the activities of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltranspeptidase. We conducted a double-blind, controlled study and used blended rapeseed oil and soybean oil (LCT) as a comparison. Two groups ingested 2,100-2,400 kcal/day of energy, 65-73 g/day of total fat, and 14 g/day of test margarine (5 g/day of MCT or LCT). The subjects on the MCT diet demonstrated significant decreases in body fat weight (-3.8 ± 2.4 kg vs -2.4 ± 1.7 kg; MCT vs LCT, mean ± SD), subcutaneous fat (-38.2 ± 29.9 cm 2 vs -22.6 ± 19.3 cm 2 ), and visceral fat (-12.2 ± 11.2 cm 2 vs -1.6 ± 12.8 cm 2 ) after 12 weeks. There were no clinical differences in measured blood parameters. We suggest that the postprandial increase in thermogenesis and control of postprandial triglyceride levels may explain these results. J Atheroscler Thromb, 2003; 10: 290-298.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.