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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3363-3370.
Prepublished online as a Blood First Edition Paper on July 25, 2006; DOI 10.1182/blood-2006-02-005520.
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IMMUNOBIOLOGY
Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8+ T-cell response
Monchou Fann,
Jason M. Godlove,
Marta Catalfamo,
William H. Wood, III,
Francis J. Chrest,
Nicholas Chun,
Larry Granger,
Robert Wersto,
Karen Madara,
Kevin Becker,
Pierre A. Henkart, and
Nan-ping Weng
From the Laboratory of Immunology, the Flow Cytometry Laboratory, the Gene Expression and Genomics Unit, and the Apheresis Unit, National Institute on Aging, National Institutes of Health, Baltimore; and the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD.
To understand the molecular basis for the rapid and robust memory T-cell responses, we examined gene expression and chromatin modification by histone H3 lysine 9 (H3K9) acetylation in resting and activated human naive and memory CD8+ T cells. We found that, although overall gene expression patterns were similar, a number of genes are differentially expressed in either memory or naive cells in their resting and activated states. To further elucidate the basis for differential gene expression, we assessed the role of histone H3K9 acetylation in differential gene expression. Strikingly, higher H3K9 acetylation levels were detected in resting memory cells, prior to their activation, for those genes that were differentially expressed following activation, indicating that hyperacetylation of histone H3K9 may play a role in selective and rapid gene expression of memory CD8+ T cells. Consistent with this model, we showed that inducing high levels of H3K9 acetylation resulted in an increased expression in naive cells of those genes that are normally expressed differentially in memory cells. Together, these findings suggest that differential gene expression mediated at least in part by histone H3K9 hyperacetylation may be responsible for the rapid and robust memory CD8+ T-cell response.
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