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dc.contributor.authorJackman, Robert W.en_US
dc.contributor.authorWu, Chia-Lingen_US
dc.contributor.authorKandarian, Susan C.en_US
dc.coverage.spatialUnited Statesen_US
dc.date2012-11-07
dc.date.accessioned2018-02-27T18:01:33Z
dc.date.available2018-02-27T18:01:33Z
dc.date.issued2012
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/23251550
dc.identifier.citationRobert W Jackman, Chia-Ling Wu, Susan C Kandarian. 2012. "The ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophy.." PLoS One, Volume 7, Issue 12, pp. e51478 - ?.
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/2144/27320
dc.description.abstractNF-kappaB transcriptional activation is required for skeletal muscle disuse atrophy. We are continuing to study how the activation of NF-kB regulates the genes that encode the protein products that cause atrophy. Using ChIP-sequencing we found that Bcl-3, an NF-kB transcriptional activator required for atrophy, binds to the promoters of a number of genes whose collective function describes two major aspects of muscle wasting. By means of bioinformatics analysis of ChIP-sequencing data we found Bcl-3 to be directing transcription networks of proteolysis and energy metabolism. The proteolytic arm of the Bcl-3 networks includes many E3 ligases associated with proteasomal protein degradation, including that of the N-end rule pathway. The metabolic arm appears to be involved in organizing the change from oxidative phosphorylation to glycolysis in atrophying muscle. For one gene, MuRF1, ChIP-sequencing data identified the location of Bcl-3 and p50 binding in the promoter region which directed the creation of deletant and base-substitution mutations of MuRF1 promoter constructs to determine the effect on gene transcription. The results provide the first direct confirmation that the NF-kB binding site is involved in the muscle unloading regulation of MuRF1. Finally, we have combined the ChIP-sequencing results with gene expression microarray data from unloaded muscle to map several direct targets of Bcl-3 that are transcription factors whose own targets describe a set of indirect targets for NF-kB in atrophy. ChIP-sequencing provides the first molecular explanation for the finding that Bcl3 knockout mice are resistant to disuse muscle atrophy. Mapping the transcriptional regulation of muscle atrophy requires an unbiased analysis of the whole genome, which we show is now possible with ChIP-sequencing.en_US
dc.description.sponsorshipR01 AR041705 - NIAMS NIH HHS; R01 AR060217 - NIAMS NIH HHS; AR041705 - NIAMS NIH HHS; AR060217 - NIAMS NIH HHSen_US
dc.format.extentp. e51478en_US
dc.languageeng
dc.relation.ispartofPLoS One
dc.rightsCopyright: © 2012 Jackman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rightshttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectScience & technologyen_US
dc.subjectN-end rule pathwayen_US
dc.subjectKappa-B P50en_US
dc.subjectDisuse atrophyen_US
dc.subjectAnimalsen_US
dc.subjectChromatin immunoprecipitationen_US
dc.subjectFemaleen_US
dc.subjectGene expression regulationen_US
dc.subjectGene regulatory networksen_US
dc.subjectGenes, reporteren_US
dc.subjectGenetic locien_US
dc.subjectGenomeen_US
dc.subjectHindlimb suspensionen_US
dc.subjectLuciferasesen_US
dc.subjectMiceen_US
dc.subjectMice, inbred C57BLen_US
dc.subjectMolecular sequence annotationen_US
dc.subjectMuscle proteinsen_US
dc.subjectMuscle, skeletalen_US
dc.subjectMuscular atrophyen_US
dc.subjectPolymerase chain reactionen_US
dc.subjectPromoter regions, geneticen_US
dc.subjectProtein bindingen_US
dc.subjectProteolysisen_US
dc.subjectProto-oncogene proteinsen_US
dc.subjectSequence analysis, DNAen_US
dc.subjectTranscription factorsen_US
dc.subjectTranscription initiation siteen_US
dc.subjectTripartite motif proteinsen_US
dc.subjectUbiquitin-protein ligasesen_US
dc.subjectWeight-bearingen_US
dc.titleThe ChIP-seq-defined networks of Bcl-3 gene binding support its required role in skeletal muscle atrophyen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0051478
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent Collegeen_US
pubs.organisational-groupBoston University, College of Health & Rehabilitation Sciences: Sargent College, Health Sciencesen_US
pubs.publication-statusPublisheden_US


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