Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells.
Memory lymphocytes are characterized by their ability to exhibit a rapid response to the recall antigen, in which differential transcription is important, yet the underlying mechanism is not understood. We report here a genome-wide analysis of histone methylation on two histone H3 lysine residues (H3K4me3 and H3K27me3) and gene expression profiles in naive and memory CD8(+) T cells. We found that specific correlation exists between gene expression and the amounts of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations displayed four distinct modes (repressive, active, poised, and bivalent), reflecting different functions of these genes in CD8(+) T cells. Furthermore, a permissive chromatin state of each gene was established by a combination of different histone modifications. Our findings reveal a complex regulation by histone methylation in differential gene expression and suggest that histone methylation may be responsible for memory CD8(+) T cell function.
Araki
Yasuto
Y
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Wang
Zhibin
Z
Zang
Chongzhi
C
Wood
William H
WH
Schones
Dustin
D
Cui
Kairong
K
Roh
Tae-Young
TY
Lhotsky
Brad
B
Wersto
Robert P
RP
Peng
Weiqun
W
Becker
Kevin G
KG
Zhao
Keji
K
Weng
Nan-ping
NP
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D002843:Chromatin / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics*; D008745:Methylation
D002843:Chromatin; D006657:Histones