Histone acetylation is associated with differential gene expression in the rapid and robust memory CD8(+) T-cell response.
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.
Fann
Monchou
M
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Godlove
Jason M
JM
Catalfamo
Marta
M
Wood
William H
WH
Chrest
Francis J
FJ
Chun
Nicholas
N
Granger
Larry
L
Wersto
Robert
R
Madara
Karen
K
Becker
Kevin
K
Henkart
Pierre A
PA
Weng
Nan-Ping
NP
D000107:Acetylation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
D016207:Cytokines; D006657:Histones