Epigenetics, bioenergetics, and microRNA coordinate gene‐specific reprogramming during acute systemic inflammation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: chromatin remodeling;    endotoxin tolerance;    facultative heterochromatin;    NAD+ ;    Nampt;    p65;    RelB;    sepsis;    sirtuin 1;    Toll‐;    like receptors;   

DOI  :  10.1189/jlb.0211075

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Acutesystemicinflammationfrominfectiousandnoninfectiousetiologieshasstereotypicfeaturesthatprogressthroughaninitiation(proinflammatory)phase,anadaptive(anti‐inflammatory)phase,andaresolution(restorationofhomeostasis)phase.Thesephase‐shiftsareaccompaniedbyprofoundandpredictablechangesingeneexpressionandmetabolism.Here,wereviewtheemergingconceptthatthetemporalphasesofacutesystemicinflammationarecontrolledbyanintegratedbioenergyandepigeneticbridgethatguidesthetimingoftranscriptionalandpost‐transcriptionalprocessesofspecificgenesets.Thisunifyingconnectiondepends,atleastinpart,onredoxsensorNAD+‐dependentdeacetylase,Sirt1,andaNF‐κB‐dependentp65andRelBfeed‐forwardandgene‐specificpathwaythatgeneratessilentfacultativeheterochromatinandactiveeuchromatin.Anadditionallevelofregulationforgene‐specificreprogrammingisgeneratedbydifferentialexpressionofmiRNAthatdirectlyandindirectlydisruptstranslationofinflammatorygenes.Thesemolecularreprogrammingcircuitsgenerateadynamicchromatinlandscapethattemporallydefinesthecourseofacuteinflammation...

【 授权许可】

CC BY