A novel, dynamic pattern-based analysis of NF-κB binding during the priming phase of liver regeneration reveals switch-like functional regulation of target genes

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Author(s)Cook, Daniel J.
Author(s)Patra, Biswanath
Author(s)Kuttippurathu, Lakshmi
Author(s)Hoek, Jan B.
Author(s)Vadigepalli, Rajanikanth
UD AuthorCook, Daniel J.en_US
UD AuthorVadigepalli, Rajanikanthen_US
Date Accessioned2015-11-30T19:23:19Z
Date Available2015-11-30T19:23:19Z
Copyright DateCopyright ©2015Cook,Patra,Kuttippurathu,HoekandVadigepalli.en_US
Publication Date2015-07-07
DescriptionPublisher's PDFen_US
AbstractFollowing partial hepatectomy, a coordinated series of molecular events occurs to regulate hepatocyte entry into the cell cycle to recover lost mass. In rats during the first 6 h following resection, hepatocytes are primed by a tightly controlled cytokine response to prepare hepatocytes to begin replication. Although it appears to be a critical element driving regeneration, the cytokine response to resection has not yet been fully characterized. Specifically, the role of one of the key response elements to cytokine signaling (NF-κB) remains incompletely characterized. In this study, we present a novel, genome-wide, pattern-based analysis characterizing NF-κB binding during the priming phase of liver regeneration. We interrogated the dynamic regulation of priming by NF-κB through categorizing NF-κB binding in different temporal profiles: immediate sustained response, early transient response, and delayed response to partial hepatectomy. We then identified functional regulation of NF-κB binding by relating the temporal response profile to differential gene expression. We found that NF-κB bound genes govern negative regulation of cell growth and inflammatory response immediately following hepatectomy. NF-κB also transiently regulates genes responsible for lipid biosynthesis and transport as well as induction of apoptosis following hepatectomy. By the end of the priming phase, NF-κB regulation of genes involved in inflammatory response, negative regulation of cell death, and extracellular structure organization became prominent. These results suggest that NF-κB regulates target genes through binding and unbinding in immediate, transient, and delayed patterns. Such dynamic switch-like patterns of NF-κB binding may govern different functional transitions that drive the onset of regeneration.en_US
DepartmentUniversity of Delaware. Department of Chemical & Biomolecular Engineering.en_US
CitationCookDJ,PatraB,KuttippurathuL, HoekJBandVadigepalliR(2015)A novel, dynamicpattern-basedanalysis of NF-kB bindingduringthepriming phase ofliverregenerationreveals switch-like functionalregulationof target genes.Front.Physiol.6:189. doi: 10.3389/fphys.2015.00189en_US
DOI10.3389/fphys.2015.00189en_US
ISSN1664-042Xen_US
URLhttp://udspace.udel.edu/handle/19716/17247
Languageen_USen_US
PublisherFrontiers Media S.A.en_US
dc.rightsCC-BY 4.0 http://creativecommons.org/licenses/by/4.0/ Required lest: This document is protected by copyright and was first published by Frontier. All rights reserved. It is reproduced with permission.en_US
dc.sourceFrontiers in Physiologyen_US
dc.source.urihttp://journal.frontiersin.org/journal/physiologyen_US
TitleA novel, dynamic pattern-based analysis of NF-κB binding during the priming phase of liver regeneration reveals switch-like functional regulation of target genesen_US
TypeArticleen_US
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