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dc.contributor.authorWu, Jennifer N.en_US
dc.contributor.authorPinello, Lucaen_US
dc.contributor.authorYissachar, Elinoren_US
dc.contributor.authorWischhusen, Jonathan W.en_US
dc.contributor.authorYuan, Guo-Chengen_US
dc.contributor.authorRoberts, Charles W. M.en_US
dc.date.accessioned2016-01-04T19:25:37Z
dc.date.issued2015en_US
dc.identifier.citationWu, Jennifer N., Luca Pinello, Elinor Yissachar, Jonathan W. Wischhusen, Guo-Cheng Yuan, and Charles W. M. Roberts. 2015. “Functionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemia.” Epigenetics & Chromatin 8 (1): 53. doi:10.1186/s13072-015-0046-0. http://dx.doi.org/10.1186/s13072-015-0046-0.en
dc.identifier.issn1756-8935en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:23993695
dc.description.abstractBackground: Precise nucleosome positioning is an increasingly recognized feature of promoters and enhancers, reflecting complex contributions of DNA sequence, nucleosome positioning, histone modification and transcription factor binding to enhancer activity and regulation of gene expression. Changes in nucleosome position and occupancy, histone variants and modifications, and chromatin remodeling are also critical elements of dynamic transcriptional regulation, but poorly understood at enhancers. We investigated glucocorticoid receptor-associated (GR) nucleosome dynamics at enhancers in acute lymphoblastic leukemia. Results: For the first time, we demonstrate functionally distinct modes of nucleosome remodeling upon chromatin binding by GR, which we term central, non-central, phased, and minimal. Central and non-central remodeling reflect nucleosome eviction by GR and cofactors, respectively. Phased remodeling involves nucleosome repositioning and is associated with rapidly activated enhancers and induction of gene expression. Minimal remodeling sites initially have low levels of enhancer-associated histone modification, but the majority of these regions gain H3K4me2 or H3K27Ac to become de novo enhancers. Minimal remodeling regions are associated with gene ontologies specific to decreased B cell number and mTOR inhibition and may make unique contributions to glucocorticoid-induced leukemia cell death. Conclusions: Our findings form a novel framework for understanding the dynamic interplay between transcription factor binding, nucleosome remodeling, enhancer function, and gene expression in the leukemia response to glucocorticoids. Electronic supplementary material The online version of this article (doi:10.1186/s13072-015-0046-0) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13072-015-0046-0en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667523/pdf/en
dash.licenseLAAen_US
dc.subjectChromatin remodelingen
dc.subjectNucleosomeen
dc.subjectGlucocorticoid receptoren
dc.subjectTranscription enhanceren
dc.subjectTranscription regulationen
dc.subjectChIP-seqen
dc.titleFunctionally distinct patterns of nucleosome remodeling at enhancers in glucocorticoid-treated acute lymphoblastic leukemiaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalEpigenetics & Chromatinen
dash.depositing.authorPinello, Lucaen_US
dc.date.available2016-01-04T19:25:37Z
dc.identifier.doi10.1186/s13072-015-0046-0*
dash.contributor.affiliatedPinello, Luca


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