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1.
Nat Immunol ; 16(10): 1034-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26322480

RESUMO

Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcription factor ATF7 in innate immunological memory. ATF7 suppressed a group of genes encoding factors involved in innate immunity in macrophages by recruiting the histone H3K9 dimethyltransferase G9a. Treatment with lipopolysaccharide, which mimics bacterial infection, induced phosphorylation of ATF7 via the kinase p38, which led to the release of ATF7 from chromatin and a decrease in repressive histone H3K9me2 marks. A partially disrupted chromatin structure and increased basal expression of target genes were maintained for long periods, which enhanced resistance to pathogens. ATF7 might therefore be important in controlling memory in cells of the innate immune system.


Assuntos
Fatores Ativadores da Transcrição/metabolismo , Epigênese Genética/imunologia , Memória Imunológica/genética , Memória Imunológica/imunologia , Macrófagos/imunologia , Fatores Ativadores da Transcrição/genética , Animais , Epigênese Genética/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
PLoS One ; 10(5): e0126967, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25974630

RESUMO

Exponential growth of high-throughput data and the increasing complexity of omics information have been making processing and interpreting biological data an extremely difficult and daunting task. Here we developed FuncTree (http://bioviz.tokyo/functree), a web-based application for analyzing and visualizing large-scale omics data, including but not limited to genomic, metagenomic, and transcriptomic data. FuncTree allows user to map their omics data onto the "Functional Tree map", a predefined circular dendrogram, which represents the hierarchical relationship of all known biological functions defined in the KEGG database. This novel visualization method allows user to overview the broad functionality of their data, thus allowing a more accurate and comprehensive understanding of the omics information. FuncTree provides extensive customization and calculation methods to not only allow user to directly map their omics data to identify the functionality of their data, but also to compute statistically enriched functions by comparing it to other predefined omics data. We have validated FuncTree's analysis and visualization capability by mapping pan-genomic data of three different types of bacterial genera, metagenomic data of the human gut, and transcriptomic data of two different types of human cell expression. All three mapping strongly confirms FuncTree's capability to analyze and visually represent key functional feature of the omics data. We believe that FuncTree's capability to conduct various functional calculations and visualizing the result into a holistic overview of biological function, would make it an integral analysis/visualization tool for extensive omics base research.


Assuntos
Interface Usuário-Computador , Bactérias/genética , Mapeamento Cromossômico , Biologia Computacional , Bases de Dados Factuais , Genoma Bacteriano , Genômica , Humanos , Internet , Intestinos/microbiologia , Metagenoma
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