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• W2166937350 abstract "Abstract The c-Myb and GATA-3 transcription factors play important roles in T cell development. We recently reported that c-Myb, GATA-3, and Menin form a core transcription complex that regulates GATA-3 expression and ultimately Th2 cell development in human peripheral blood T cells. However, c-Myb roles for Th2 cytokine expression were not demonstrated. In this article, we report that c-Myb and GATA-3 cooperatively play an essential role in IL-13 expression though direct binding to a conserved GATA-3 response element (CGRE), an enhancer for IL-13 expression. c-Myb and GATA-3 were shown to activate the CGRE–IL-13 promoter by ∼160-fold, and mutation of the canonical Myb binding site completely abrogated CGRE enhancer activity. In contrast, mutation of the GATA binding site partially decreased CGRE enhancer activity. GATA-3 did not bind to CGRE when c-myb expression was silenced. c-Myb, GATA-3, Menin, and mixed lineage leukemia (MLL) bound to CGRE in human primary CD4+ effector/memory cells. Moreover, c-myb silencing significantly decreased both methylation of histone H3K4 and acetylation of histone H3K9 at the IL-13 locus in CD4+ effector/memory cells. Therefore, in addition to the strong enhancer effect for the transcription of IL-13, the c-Myb/GATA-3 complex recruits MLL to the CGRE for histone modification of the IL-13 locus during the differentiation of memory Th2 cells." @default.
• W2166937350 created "2016-06-24" @default.
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• W2166937350 date "2011-12-01" @default.
• W2166937350 modified "2023-10-18" @default.
• W2166937350 title "c-Myb and GATA-3 Cooperatively Regulate IL-13 Expression via Conserved GATA-3 Response Element and Recruit Mixed Lineage Leukemia (MLL) for Histone Modification of the IL-13 Locus" @default.
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• W2166937350 doi "https://doi.org/10.4049/jimmunol.1100550" @default.
• W2166937350 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3221810" @default.
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