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dc.contributor.authorLeBlanc, Scott E.
dc.contributor.authorWu, Qiong
dc.contributor.authorBarutcu, A. Rasim
dc.contributor.authorXiao, Hengyi
dc.contributor.authorOhkawa, Yasuyuki
dc.contributor.authorImbalzano, Anthony N.
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:18:36Z
dc.date.available2022-08-23T16:18:36Z
dc.date.issued2014-01-20
dc.date.submitted2014-06-10
dc.identifier.citation<p>LeBlanc SE, Wu Q, Barutcu AR, Xiao H, Ohkawa Y, Imbalzano AN. The PPARγ locus makes long-range chromatin interactions with selected tissue-specific gene loci during adipocyte differentiation in a protein kinase A dependent manner. PLoS One. 2014 Jan 20;9(1):e86140. doi: 10.1371/journal.pone.0086140. <a href="http://dx.doi.org/10.1371/journal.pone.0086140">Link to article on publisher's site</a></p>
dc.identifier.issn1932-6203 (Linking)
dc.identifier.doi10.1371/journal.pone.0086140
dc.identifier.pmid24465921
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34857
dc.description.abstractDifferentiation signaling results in reprogramming of cellular gene expression that leads to morphological changes and functional specialization of a precursor cell. This global change in gene expression involves temporal regulation of differentiation-specific genes that are located throughout the genome, raising the idea that genome structure may also be re-organized during cell differentiation to facilitate regulated gene expression. Using in vitro adipocyte differentiation as a model, we explored whether gene organization within the nucleus is altered upon exposure of precursor cells to signaling molecules that induce adipogenesis. The peroxisome proliferator-activated receptor gamma (PPARgamma) nuclear hormone receptor is a master determinant of adipogenesis and is required for adipose differentiation. We utilized the chromosome conformation capture (3C) assay to determine whether the position of the PPARgamma locus relative to other adipogenic genes is changed during differentiation. We report that the PPARgamma2 promoter is transiently positioned in proximity to the promoters of genes encoding adipokines and lipid droplet associated proteins at 6 hours post-differentiation, a time that precedes expression of any of these genes. In contrast, the PPARgamma2 promoter was not in proximity to the EF1alpha promoter, which drives expression of a constitutively active, housekeeping gene that encodes a translation elongation factor, nor was the PPARgamma2 promoter in proximity to the promoter driving the expression of the C/EBPalpha regulatory protein. The formation of the long-range, intergenic interactions involving the PPARgamma2 promoter required the regulatory factor C/EBPbeta, elevated cyclic AMP (cAMP) levels, and protein kinase A (PKA) signaling. We conclude that genome organization is dynamically remodeled in response to adipogenic signaling, and we speculate that these transient inter-genic interactions may be formed for the purposes of selecting some of the transcriptionally silent tissue-specific loci for subsequent transcriptional activation.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=24465921&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rights<p>Copyright 2014 LeBlanc et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular Genetics
dc.titleThe PPARgamma locus makes long-range chromatin interactions with selected tissue-specific gene loci during adipocyte differentiation in a protein kinase A dependent manner
dc.typeJournal Article
dc.source.journaltitlePloS one
dc.source.volume9
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1017&amp;context=imbalzano&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/imbalzano/17
dc.identifier.contextkey5676454
refterms.dateFOA2022-08-23T16:18:37Z
html.description.abstract<p>Differentiation signaling results in reprogramming of cellular gene expression that leads to morphological changes and functional specialization of a precursor cell. This global change in gene expression involves temporal regulation of differentiation-specific genes that are located throughout the genome, raising the idea that genome structure may also be re-organized during cell differentiation to facilitate regulated gene expression. Using in vitro adipocyte differentiation as a model, we explored whether gene organization within the nucleus is altered upon exposure of precursor cells to signaling molecules that induce adipogenesis. The peroxisome proliferator-activated receptor gamma (PPARgamma) nuclear hormone receptor is a master determinant of adipogenesis and is required for adipose differentiation. We utilized the chromosome conformation capture (3C) assay to determine whether the position of the PPARgamma locus relative to other adipogenic genes is changed during differentiation. We report that the PPARgamma2 promoter is transiently positioned in proximity to the promoters of genes encoding adipokines and lipid droplet associated proteins at 6 hours post-differentiation, a time that precedes expression of any of these genes. In contrast, the PPARgamma2 promoter was not in proximity to the EF1alpha promoter, which drives expression of a constitutively active, housekeeping gene that encodes a translation elongation factor, nor was the PPARgamma2 promoter in proximity to the promoter driving the expression of the C/EBPalpha regulatory protein. The formation of the long-range, intergenic interactions involving the PPARgamma2 promoter required the regulatory factor C/EBPbeta, elevated cyclic AMP (cAMP) levels, and protein kinase A (PKA) signaling. We conclude that genome organization is dynamically remodeled in response to adipogenic signaling, and we speculate that these transient inter-genic interactions may be formed for the purposes of selecting some of the transcriptionally silent tissue-specific loci for subsequent transcriptional activation.</p>
dc.identifier.submissionpathimbalzano/17
dc.contributor.departmentDepartment of Cell and Developmental Biology
dc.source.pagese86140


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<p>Copyright 2014 LeBlanc et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
Except where otherwise noted, this item's license is described as <p>Copyright 2014 LeBlanc et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>