The genomic landscape of histone modifications in human T cells
- Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
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Communicated by Carl Wu, National Institutes of Health, Bethesda, MD, September 5, 2006 (received for review June 23, 2006)
Abstract
To understand the molecular basis that supports the dynamic gene expression programs unique to T cells, we investigated the genomic landscape of activating histone modifications, including histone H3 K9/K14 diacetylation (H3K9acK14ac), H3 K4 trimethylation (H3K4me3), and the repressive histone modification H3 K27 trimethylation (H3K27me3) in primary human T cells. We show that H3K9acK14ac and H3K4me3 are associated with active genes required for T cell function and development, whereas H3K27me3 is associated with silent genes that are involved in development in other cell types. Unexpectedly, we find that 3,330 gene promoters are associated with all of these histone modifications. The gene expression levels are correlated with both the absolute and relative levels of the activating H3K4me3 and the repressive H3K27me3 modifications. Our data reveal that rapidly inducible genes are associated with the H3 acetylation and H3K4me3 modifications, suggesting they assume a chromatin structure poised for activation. In addition, we identified a subpopulation of chromatin regions that are associated with high levels of H3K4me3 and H3K27me3 but low levels of H3K9acK14ac. Therefore, these regions have a distinctive chromatin modification pattern and thus may represent a distinct class of chromatin domains.
Footnotes
- *To whom correspondence should be addressed at: Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N311, 9000 Rockville Pike, Bethesda, MD 20892. E-mail: zhaok{at}nhlbi.nih.gov
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Author contributions: T.-Y.R. and S.C. contributed equally to this work. T.-Y.R., S.C., and K.Z. designed research; T.-Y.R., S.C., and K.Z. performed research; K.C. contributed new reagents/analytic tools; T.-Y.R., S.C., K.C., and K.Z. analyzed data; and T.-Y.R., S.C., and K.Z. wrote the paper.
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The authors declare no conflict of interest.
- Abbreviations:
- GMAT,
- genome-wide mapping technique;
- ChIP,
- chromatin immunoprecipitation;
- TSS,
- transcription start site;
- TCR,
- T cell receptor.
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Freely available online through the PNAS open access option.
