Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T cells

组蛋白甲基化的全基因组分析揭示了染色质状态对基因转录和记忆 CD8+ T 细胞功能的调控

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作者:Yasuto Araki, Zhibin Wang, Chongzhi Zang, William H Wood 3rd, Dustin Schones, Kairong Cui, Tae-Young Roh, Brad Lhotsky, Robert P Wersto, Weiqun Peng, Kevin G Becker, Keji Zhao, Nan-ping Weng

Abstract

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.

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