Effect of Promoter Methylation on
the Regulation of IFN- Gene During In
Vitro Differentiation of Human
Peripheral Blood T Cells into a Th2
Population
作者：Shingo Yano, Paritosh Ghosh, Hitoshi Kusaba, Meredith Buchholz and
Dan L. Longo
作者单位：Lymphocyte Cell Biology Section, Laboratory of Immunology,
Gerontology Research Center, National Institute on Aging, National
Institutes of Health, Baltimore, MD 21224
【摘要】
The carefully orchestrated events that result in a protective
immune response are coordinated to a large extent by cytokines produced
by Th1 and Th2 cell subsets. Th1 cells preferentially produce IL-2 and
IFN-, resulting in a cellular response that helps to eliminate infected
cells. In contrast, Th2 cells produce IL-4, IL-5, IL-6, and IL-10,
stimulating an Ab response that attacks extracellular pathogens, thereby
preventing the cells from becoming infected. To elucidate the mechanisms
of differential regulation of cytokine genes by these two different
subsets of T cells, we established an in vitro differentiation model of
freshly isolated human peripheral blood T cells in which IFN- was used
as an index gene to study the transcriptional regulation. The data
presented here demonstrate that the IFN- promoter undergoes differential
methylation during in vitro differentiation: the promoter becomes
hypermethylated in Th2 cells, whereas it is hypomethylated in Th1 cells.
Hypermethylation in Th2 cells results in chromatin condensation and
exclusion of CREB proteins from the IFN- promoter. Treatment with
5-azacytidine, a demethylating agent, causes Th2 cells to reverse histone
condensation and enables CREB recruitment to the hypomethylated promoter.
This results in the increased production of IFN-. These data indicate the
importance of promoter methylation in the regulation of the IFN - gene
during differentiation.
【关键词】
Population
Promoter Methylation Regulation Differentiation Peripheral
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