Show simple item record

dc.contributor.authorChin, Hang Gyeongen_US
dc.contributor.authorPonnaluri, V. K. Chaithanyaen_US
dc.contributor.authorZhang, Guoqiangen_US
dc.contributor.authorEsteve, Pierre-Olivieren_US
dc.contributor.authorSchaus, Scott E.en_US
dc.contributor.authorHansen, Ullaen_US
dc.contributor.authorPradhan, Sriharsaen_US
dc.date.accessioned2020-05-04T15:11:18Z
dc.date.available2020-05-04T15:11:18Z
dc.date.issued2016-12-13
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000391352800133&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e74115fe3da270499c3d65c9b17d654
dc.identifier.citationHang Gyeong Chin, VK Chaithanya Ponnaluri, Guoqiang Zhang, Pierre-Olivier Esteve, Scott E Schaus, Ulla Hansen, Sriharsa Pradhan. 2016. "Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression." ONCOTARGET, Volume 7, Issue 50, pp. 83627 - 83640 (14). https://doi.org/10.18632/oncotarget.13271
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/2144/40527
dc.description.abstractThe transcription factor LSF is highly expressed in hepatocellular carcinoma (HCC) and promotes oncogenesis. Factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity and exerts anti-proliferative activity. Here, we show that LSF binds directly to the maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1) and its accessory protein UHRF1 both in vivo and in vitro. Binding of LSF to DNMT1 stimulated DNMT1 activity and FQI1 negated the methyltransferase activation. Addition of FQI1 to the cell culture disrupted LSF bound DNMT1 and UHRF1 complexes, resulting in global aberrant CpG methylation. Differentially methylated regions (DMR) containing at least 3 CpGs, were significantly altered by FQI1 compared to control cells. The DMRs were mostly concentrated in CpG islands, proximal to transcription start sites, and in introns and known genes. These DMRs represented both hypo and hypermethylation, correlating with altered gene expression. FQI1 treatment elicits a cascade of effects promoting altered cell cycle progression. These findings demonstrate a novel mechanism of FQI1 mediated alteration of the epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression.en_US
dc.description.sponsorshipWe would like to thank Drs. Donald Comb, Rich Roberts, William Jack and Clotilde Carlow at New England Biolabs Inc. for research support and encouragement. The authors thank Dr. Lauren Brown (Boston University Center for Molecular Discovery) for the preparation of FQI1. UH research on this project was supported by Ignition Awards from Boston University and a Johnson & Johnson Clinical Innovator's Award through Boston University. SES research is supported by the NIH (P50 GM067041 & R24 GM111625). Research performed by HGC was partly a requirement for the MCBB graduate program at Boston University and supported by NEB. (Boston University; Johnson & Johnson Clinical Innovator's Award through Boston University; P50 GM067041 - NIH; R24 GM111625 - NIH; NEB)en_US
dc.format.extentp. 83627 - 83640en_US
dc.languageEnglish
dc.language.isoen_US
dc.publisherIMPACT JOURNALS LLCen_US
dc.relation.ispartofONCOTARGET
dc.rightsThis article is made available under a Creative Commons Attribution 3.0 License.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectOncologyen_US
dc.subjectCell biologyen_US
dc.subjectDNA methylationen_US
dc.subjectTranscription factor LSFen_US
dc.subjectGene expressionen_US
dc.subjectHCCen_US
dc.subjectSmall-molecule inhibitorsen_US
dc.subjectFactor LSFen_US
dc.subjectCytosine-5 methyltransferaseen_US
dc.subjectRepresses transcriptionen_US
dc.subjectOncogeneen_US
dc.subjectDNMT1en_US
dc.subjectHypermethylationen_US
dc.subjectProgressionen_US
dc.subjectMechanismen_US
dc.subjectCloningen_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic agentsen_US
dc.subjectBenzodioxolesen_US
dc.subjectCCAAT-enhancer-binding proteinsen_US
dc.subjectCOS cellsen_US
dc.subjectCarcinoma, hepatocellularen_US
dc.subjectCell cycleen_US
dc.subjectCell proliferationen_US
dc.subjectChlorocebus aethiopsen_US
dc.subjectCpG islandsen_US
dc.subjectDNA (cytosine-5-)-methyltransferase 1en_US
dc.subjectDNA-binding proteinsen_US
dc.subjectEpigenesis, geneticen_US
dc.subjectGene expression regulation, neoplasticen_US
dc.subjectHEK293 cellsen_US
dc.subjectHumansen_US
dc.subjectLiver neoplasmsen_US
dc.subjectProtein bindingen_US
dc.subjectQuinolonesen_US
dc.subjectTranscription factorsen_US
dc.subjectTransfectionen_US
dc.subjectOncology and carcinogenesisen_US
dc.titleTranscription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expressionen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.18632/oncotarget.13271
pubs.elements-sourceweb-of-scienceen_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Biologyen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublisheden_US
dc.identifier.mycv120240


This item appears in the following Collection(s)

Show simple item record

This article is made available under a Creative Commons Attribution 3.0 License.
Except where otherwise noted, this item's license is described as This article is made available under a Creative Commons Attribution 3.0 License.