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Special AT-rich binding protein 1(SATB1) is a global genomic organizer that integrates higher-order chromatin organization with regulation of gene expression.Aberrant expression of SATB 1 has been associated with various cancers.Disruption of apoptosis is one of a hallmark of cancer.However, the intrinsic link between SATB 1 and regulation of apoptosis still has to be elucidated.Our previous study has found that the major break point region (mbr) located within 3-UTR of the BCL2 gene is a regulatory element.SATB1 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 SATBl-mediated chromatin loop conformation in regulation of apoptosis.In 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 18.We demonstrated that the SATB 1 bound site within NOXA gene was specially juxtaposed with both mbr element and BCL2 promoter through SATB 1-mediated chromatin-loop conformation in Jurkat cells with chromosome conformation capture (3C) and chromatin immuneprecipitation (ChIP) assays.The SATB 1-mediated BCL2 and NOXA chromatin loop conformation was required for coordinated expression of these two distinct BCL2 family members.Down-regulation of SATB 1 expression induced disassembly of mbr-BCL2 chromatin loop and increased assembly of mbr-NOXA chromatin loops.Alteration of SATB 1 levels resulted in switch between mbr-BCL2 and mbr-NOXA chromatin loops and thus changed expression levels of the genes accordingly.During early apoptosis SATB 1 coordinated expression of BCL2 and NOXA genes through mediating dynamic change in long-range chromatin interactions.The role of SATB 1 was very specific, since transfection with mutant SATB 1 resistant to caspase-6 or treatment with caspase-6 inhibitor restored BCL-2 expression and reduced NOXA levels in Jurkat cells.These data indicated that SATB1 was an important determinant for coordinated expression of anti-apoptotic BCL2 gene and pro-apoptotic NOXA gene in response of cells to apoptotic stimuli.