Epigenetic modification controls the response of insm1b to RA signaling in zebrafish early developme

• 作 者: Xiaohua Dong Wenshuang Jia Dong Liang Jingyun Li Qingshun Zhao
• 机 构: ModelAnimalResearchCenter,MOEKeyLaboratoryofModelAnimalforDiseaseStudy,NanjingUniversity,Nanjing2100
• 出 处: 第三届全国斑马鱼研究大会
• 发表日期: 2013年10期
• 关键词: zebrafish insm1b retinoic acid retinoic acid response element hdac1

　　Retinoic acid(RA)signaling plays crucial roles in early embryonic development of vertebrates through the ligand,RA,binding to the heterodimers of RA receptors(RARs)and retinoid-X receptors(RXRs)to regulate expression of target genes containing RA response elements(RAREs).Transcriptions of hundreds of genes have been reported to be influenced by RA signaling;however,no more than 70 genes have been identified to be its direct target genes with RAREs in their regulatory region.Administrating zebrafish embryos with exogenous RA,we found that insm1b(insulinoma-associated 1b)was significantly induced to express in the embryos at blastula stage.Results from the assays on the promoter revealed that insm1b owns a conserved DR1 RARE in its regulatory region that is in response to RA signaling.However,the expression of insm1b was little induced by exogenous RA during gastrula stage.Treating the embryos with TSA(trichostatin A),the inhibitor of HDACs(histone deacetylase),resumed the response of embryos to exogenous RA signaling.ChIP assay demonstrated that hdac1 is involved in the epigenetic modification of insm1b to mask its sensitive to exogenous RA signaling.Taken together,our results show that insm1b is a direct target gene of RA signaling and epigenetic modification controls the response of insm1b to RA signaling in zebrafish early development.