Genome-wide Analysis of Histone Methylation Reveals Chromatin State-Based Regulation of Gene Transcription and Function of Memory CD8+ T Cells

Abstract

Summary Memory lymphocytes are characterized by their ability to exhibit a rapid response to the recall antigen, in which differential transcription plays a significant role, 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 naïve and memory CD8 T cells. We found that a general correlation exists between the levels of gene expression and the levels of H3K4me3 (positive correlation) and H3K27me3 (negative correlation) across the gene body. These correlations display four distinct modes: repressive, active, poised, and bivalent, reflecting different functions of these genes. Furthermore, a permissive chromatin state of each gene is 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.

Histone Acetylation at the Single-Cell Level: A Marker of Memory CD8+ T Cell Differentiation and Functionality

“…All plots are representative of and values are compiled from three independent experiments with three to four mice per group. functionality (3,7). Although histone modifications are numerous and an essential component of chromatin structure, relationships between the abundance and/or pattern of specific marks and CD8 + T cell differentiation state are largely unknown.…”

“…Specifically, when a well-defined set of loci is known to be functionally important for the lineages under study, these loci can be analyzed in a targeted manner using chromatin immunoprecipitation (ChIP) followed by quantitative PCR using locus-specific primers (6). Alternatively, the advent of genomic DNA arrays and high-throughput DNA sequencing has allowed unbiased analyses of genomic fragments recovered by ChIP (7,8). Although these techniques have greatly facilitated genome-wide mapping of specific hPTMs, they are still dependent on large numbers of cells, which poses a challenge for studying rare populations, such as Ag-specific T M cells.…”

Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells

“…Using chromatin immunoprecipitation combined with genome-wide DNA sequencing (ChIPseq), they mapped the density of two histone H3 modifications: tri-methylation of lysine 4 (a mark associated with open chromatin) and tri-methylation of lysine 27 (a mark of closed chromatin) [61]. Within this rich data set, two observations stand out.…”

Global Analysis of O-GlcNAc Glycoproteins in Activated Human T Cells

“…In addition to tyrosine phosphorylation, a variety of other posttranslational modifications are involved in the regulation of T cell activation, a process that must be strictly controlled to permit appropriate responses against foreign Ags while preventing inappropriate responses to self-antigens. Canonical examples include serine/threonine phosphorylation, lysine methylation and acetylation, lysine ubiquitylation, and cysteine palmitoylation, which can influence transcription factor activation, chromatin accessibility, protein stability, and membrane localization, respectively (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”