Submitted February 23, 2006
Accepted June 23, 2006
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*
National Institute on Aging, National Institutes of Health, Baltimore, MD
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda,
Gene Expression and Genomics Unit, Baltimore, MD
Flow Cytometry Laboratory, Baltimore, MD
Apharesis Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD
* Corresponding author; email: wengn{at}mail.nih.gov.
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 naïve 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 the 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.
