Abstract
The role of chromatin remodeling and histone posttranslational modifications and how they are integrated to control gene expression during the acquisition of cell-specific functions is poorly understood. We show here that following in vitro activation of CD4(+) and CD8(+) T lymphocytes, both cell types show rapid histone H3 loss at the granzyme B (gzmB) proximal promoter region. However, despite the gzmB proximal promoter being remodeled in both T cell subsets, only CD8(+) T cells express high levels of gzmB and display a distinct pattern of key epigenetic marks, notably differential H3 acetylation and methylation. These data suggest that for high levels of transcription to occur a distinct set of histone modifications needs to be established in addition to histone loss at the proximal promoter of gzmB.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / metabolism*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Differentiation / immunology
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Cell Lineage
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Chromatin Assembly and Disassembly*
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Epigenesis, Genetic*
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Flow Cytometry
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Gene Expression
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Gene Expression Regulation / immunology
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Granzymes / biosynthesis
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Granzymes / genetics*
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Histones / metabolism
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Lymphocyte Activation / genetics
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Mice
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Microscopy, Confocal
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Oligonucleotide Array Sequence Analysis
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Promoter Regions, Genetic
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RNA Polymerase II / genetics
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RNA Polymerase II / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / metabolism*
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Transcription, Genetic
Substances
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Histones
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RNA Polymerase II
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Granzymes