SATB1 Mediates Long-Range Chromatin Interactions: A Dual Regulator of Anti-Apoptotic BCL2 and Pro-Apoptotic NOXA Genes

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dc.contributor.authorYin Yang
dc.contributor.authorZongdan Wang
dc.contributor.authorLuan Sun
dc.contributor.authorLipei Shao
dc.contributor.authorNan Yang
dc.contributor.authorDawei Yu
dc.contributor.authorXin Zhang
dc.contributor.authorXiao Han
dc.contributor.authorYujie Sun
dc.date.accessioned2017-03-05T22:55:19Z
dc.date.available2017-03-05T22:55:19Z
dc.date.issued2015-09-30
dc.descriptionWe thank Ms. Kathy Kyler for her kind help in English editing of the manuscript.en_US
dc.descriptionen_US
dc.description.abstractAberrant expression of special AT-rich binding protein 1 (SATB1), a global genomic organizer, has been associated with various cancers, which raises the question of how higher-order chromatin structure contributes to carcinogenesis. Disruption of apoptosis is one of the hallmarks of cancer. We previously demonstrated that SATB1 mediated specific long-range chromosomal interactions between the mbr enhancer located within 3’-UTR of the BCL2 gene and the promoter to regulate BCL2 expression during early apoptosis. In the present study, we used chromosome conformation capture (3C) assays and molecular analyses to further investigate the function of the SATB1-mediated higher-order chromatin structure in co-regulation of the anti-apoptotic BCL2 gene and the pro-apoptotic NOXA gene located 3.4Mb downstream on Chromosome 18. We demonstrated that the mbr enhancer spatially juxtaposed the promoters of BCL2 and NOXA genes through SATB1-mediated chromatin-loop in Jurkat cells. Decreased SATB1 levels switched the mbr-BCL2 loop to mbr-NOXA loop, and thus changed expression of these two genes. The SATB1-mediated dynamic switch of the chromatin loop structures was essential for the cooperative expression of the BCL2 and NOXA genes in apoptosis. Notably, the role of SATB1 was specific, since inhibition of SATB1 degradation by caspase-6 inhibitor or caspase-6-resistant SATB1 mutant reversed expression of BCL-2 and NOXA in response to apoptotic stimulation. This study reveals the critical role of SATB1-organized higher-order chromatin structure in regulating the dynamic equilibrium of apoptosis-controlling genes with antagonistic functions and suggests that aberrant SATB1 expression might contribute to cancer development by disrupting the co-regulated genes in apoptosis pathways.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationYang Y, Wang Z, Sun L, Shao L, Yang N, Yu D, et al. (2015) SATB1 Mediates Long-Range Chromatin Interactions: A Dual Regulator of Anti-Apoptotic BCL2 and Pro-Apoptotic NOXA Genes. PLoS ONE 10(9): e0139170. doi:10.1371/journal.pone.0139170en_US
dc.identifier.doi10.1371/journal.pone.0139170en_US
dc.identifier.urihttp://hdl.handle.net/11244/49277
dc.language.isoen_USen_US
dc.publisherPLos One
dc.relation.ispartofseriesPLoS ONE 10(9): e0139170
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0139170
dc.rightsAttribution 3.0 United States
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/
dc.subjectChromatin,Apoptosis,Gene regulation,Gene expression,Polymerase chain reaction,DNA transcription,Transcription factors,Chromosomesen_US
dc.titleSATB1 Mediates Long-Range Chromatin Interactions: A Dual Regulator of Anti-Apoptotic BCL2 and Pro-Apoptotic NOXA Genesen_US
dc.typeResearch Articleen_US

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