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The role of SATBl-mediated chromatin loop conformation in re...

The role of SATBl-mediated chromatin loop conformation in regulation of coordinated expression of anti-apoptotic BCL2 and pro-apoptotic NOXA genes

作     者:Zongdan Wang Yin Yang Lipei Shao Luan Sun Nan Yang Xiao Han 孙玉洁 

作者单位:Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Cell BiologyNanjing Medical University 

会议名称:《遗传学与表观遗传学前沿暨第三届中国青年遗传学家论坛》

会议日期:2014年

学科分类:0710[理学-生物学] 07[理学] 08[工学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

关 键 词:Chromatin loop SATB1 BCL2 NOXA 

摘      要:Special AT-rich binding protein 1(SATB1)is a global genomic organizer that integrates higher-order chromatin organization with regulation of gene *** expression of SATB1 has been associated with various *** of apoptosis is one of a hallmark of ***,the intrinsic link between SATB1 and regulation of apoptosis still has to be *** previous study has found that the major break point region(mbr)located within3’-UTR of the BCL2 gene is a regulatory ***1 mediates specific long-range chromosomal interaction between the mbr and BCL-2 promoter to regulate the BCL2 expression during early apoptosis,which highlighted the role of SATB1-mediated chromatin loop conformation in regulation of *** this study we searched new target genes of the mbr within BCL2 family members and investigated the role of SATB1 in regulating coordinated expression of anti-apoptotic BCL2 gene and pro-apoptotic NOXA gene that are 3.4Mb away on Chromosome *** demonstrated that the SATB1 bound site within NOXA gene was specially juxtaposed with both mbr element and BCL2 promoter through SATB1-mediated chromatin-loop conformation in Jurkat cells with chromosome conformation capture(3C)and chromatin immuneprecipitation(ChIP)*** SATB1-mediated BCL2 and NOXA chromatin loop conformation was required for coordinated expression of these two distinct BCL2 family ***-regulation of SATB1 expression induced disassembly of mbr-BCL2 chromatin loop and increased assembly of mbr-NOXA chromatin *** of SATB1 levels resulted in switch between mbr-BCL2 and mbr-NOXA chromatin loops and thus changed expression levels of the genes *** early apoptosis SATB1 coordinated expression of BCL2 and NOXA genes through mediating dynamic change in long-range chromatin *** role of SATB1 was very specific,since transfection with mutant SATB1 resistant to caspase-6 or treatment with caspase-6 inhibitor restored BCL-

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