Gfi‐1 is the transcriptional repressor of SOCS1 in acute myeloid leukemia cells

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

关键词: G9a;    SUV39H1;    H3K9 methylation;   

DOI  :  10.1189/jlb.0912475

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

SilencingofSOCS1,aTSG,hasbeendetectedinvariousmalignancies,includingAML.However,theunderlyingmechanismofSOCS1inactivationremainselusive.Inthisstudy,weexploredtheroleofhistonemethylationinSOCS1expressioninAMLcells.ByChIPassay,wedemonstratedthatG9aandSUV39H1,twoenzymescatalyzingH3K9methylation,werephysicallyassociatedwiththeSOCS1promoter,andtreatmentwithchaetocin,ahistonemethyltransferaseinhibitor,suppressedH3K9methylationontheSOCS1promoterandenhancedSOCS1expression.Furthermore,knockdownofG9aandSUV39H1bysiRNAcouldalsoinduceSOCS1expression.Ontheotherhand,SOCS1knockdownbyshRNAeliminatedchaetocin‐inducedcellapoptosis.ToinvestigatefurtherwhetheranytranscriptionfactorwasinvolvedinH3K9methylation‐relatedSOCS1repression,wescannedthesequencesoftheSOCS1genepromoterandfoundtwobindingsitesforGfi‐1,atranscriptionrepressor.ByDNApull‐downandChIPassays,weshowedthatGfi‐1directlyboundtheSOCS1promoter,andectopicGfi‐1expressionsuppressedSTAT5‐inducedSOCS1promoteractivation.Incontrast,Gfi‐1knockdownbyshRNAenhancedSOCS1expressionandinhibitedSTAT5expression.Moreover,theknockdownofG9acompletelyrescuedtherepressiveeffectofGfi‐1onSTAT5A‐inducedSOCS1promoteractivation.Collectively,ourstudyindicatesthattheexpressionofGfi‐1contributestoSOCS1silencinginAMLcellsthroughepigeneticmodification,andsuppressionofhistonemethyltransferasecanprovidenewinsightinAMLtherapy...

【 授权许可】

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