Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from P14 TCR cytotoxic T cells overexpressing HDAC7 phosphorylation deficient mutant

ABSTRACT: The present study reports an unbiased analysis of the cytotoxic T cell serine-threonine phosphoproteome using high resolution mass spectrometry. Approximately 2,000 phosphorylations were identified in CTLs of which approximately 450 were controlled by TCR signaling. A significantly overrepresented group of molecules identified in the phosphoproteomic screen were transcription activators, co-repressors and chromatin regulators. A focus on the chromatin regulators revealed that CTLs have high expression of the histone deacetylase HDAC7 but continually phosphorylate and export this transcriptional repressor from the nucleus. HDAC7 dephosphorylation results in its nuclear accumulation and suppressed expression of genes encoding key cytokines, cytokine receptors and adhesion molecules that determine CTL function. The screening of the CTL phosphoproteome thus reveals intrinsic pathways of serine-threonine phosphorylation that target chromatin regulators in CTLs and determine the CTL functional program. We used Affymetrix microarray analysis to explore the molecular basis for the role of HDAC7 in CTLs and the impact of GFP-HDAC7 phosphorylation deficient mutant expression on the CTL transcriptional profile. In vitro generated P14 TCR cytotoxic T cells were retrovirally infected with a construct encoding GFP-HDAC7 phosphorylation deficient mutant, sorted in base of GFP expression (GFP positive and GFP negative) and processed for microarray analysis in three biological replicas.

ORGANISM(S): Mus musculus

SUBMITTER: Maria Navarro

PROVIDER: E-GEOD-27092 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes.

Navarro Maria N MN Goebel Jurgen J Feijoo-Carnero Carmen C Morrice Nick N Cantrell Doreen A DA

Nature immunology 20110313 4

Here we report an unbiased analysis of the cytotoxic T lymphocyte (CTL) serine-threonine phosphoproteome by high-resolution mass spectrometry. We identified approximately 2,000 phosphorylations in CTLs, of which approximately 450 were controlled by T cell antigen receptor (TCR) signaling. A significantly overrepresented group of molecules identified included transcription activators, corepressors and chromatin regulators. A focus on chromatin regulators showed that CTLs had high expression of th ...[more]

PMID: 21399638

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Project description:Obesity and its consequences on cardiometabolic health have been associated to low-grade inflammation. The most diverse source of dietary anti-inflammatory compounds is polyphenols and especially anthocyanins, which are major polyphenols in bilberries (Vaccinium myrtillus). We investigated the effects of a bilberry-rich diet on glucose and lipid metabolism, inflammation and gene expression profile in peripheral blood mononuclear cells (PBMCs) in subjects with overweight and other features of the metabolic syndrome. The study was a randomized, controlled clinical intervention using 2-arm parallel group design. The participants in the bilberry group (BB, n = 15) consumed bilberries or berry products equivalent of 400 g fresh bilberries daily for 8 weeks, while the participants in the control group (C, n = 12) were asked to maintain their habitual diet. The microarray profiling was done from 3 subjects in the BB group and further QPCR expression analyses from all subjects in both groups at the start and end of the intervention (weeks 0 and 8). From 50 differentially expressed transcripts (P<0.005), five candidate genes; WDSUB1, COX7B, RGS18, DAPP1 and TICAM1, were randomly selected for QPCR analyses from PBMCs in both groups. To further explore the interplay of dietary change and activated pathways in PBMCs, 11 additional genes were selected for QPCR. The selected transcripts were from the LPB, RIPK-1, Ly96 (MD2), CD19, MMD, TNFRSF12A, CD72, CCR2, IL17RC, IL17R and MAP3K7IP2 genes. Our results indicate that regular bilberry intake may reduce endotoxemia and chronic inflammation, the latter especially by directing the immunity away from overactive innate cell mediated responsiveness. Bilberry consumption may decrease cardiovascular and metabolic risk in the long term. The microarray profiling was done in PBMCs from 3 subjects in BB group and further QPCR expression analyses in PBMCs from 15 subjects in the BB group and 12 subjects in the C group. For QPCR expression analyses; Time point (biological replicate): 0 wk: baseline PBMCs1 - 15, baseline PBMCc1- 12 Time point (biological replicate): 8 wk: bilberry PBMCs1 - 15, bilberry PBMCc1 - 12 Non-normalized data with triplicate samples (technical replicate) of each bilogical replicates (replicate1-3)

Dataset Information

Expression data from P14 TCR cytotoxic T cells overexpressing HDAC7 phosphorylation deficient mutant

Publications

Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes.

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