FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2895522259> ?p ?o ?g. }

• W2895522259 endingPage "2620" @default.
• W2895522259 startingPage "2608" @default.
• W2895522259 abstract "Epigenetic regulation of gene expression has been implicated in the pathogenesis of obesity and type 2 diabetes. However, detailed information, such as key transcription factors in pancreatic beta cells that mediate environmental effects, is not yet available.To analyse genome-wide cis-regulatory profiles and transcriptome of pancreatic islets derived from a diet-induced obesity (DIO) mouse model, we conducted chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) of histone H3 lysine 27 acetylation (histone H3K27ac) and high-throughput RNA sequencing. Transcription factor-binding motifs enriched in differential H3K27ac regions were examined by de novo motif analysis. For the predicted transcription factors, loss of function experiments were performed by transfecting specific siRNA in INS-1, a rat beta cell line, with and without palmitate treatment. Epigenomic and transcriptional changes of possible target genes were evaluated by ChIP and quantitative RT-PCR.After long-term feeding with a high-fat diet, C57BL/6J mice were obese and mildly glucose intolerant. Among 39,350 islet cis-regulatory regions, 13,369 and 4610 elements showed increase and decrease in ChIP-Seq signals, respectively, significantly associated with global change in gene expression. Remarkably, increased H3K27ac showed a distinctive genomic localisation, mainly in the proximal-promoter regions, revealing enriched elements for nuclear respiratory factor 1 (NRF1), GA repeat binding protein α (GABPA) and myocyte enhancer factor 2A (MEF2A) by de novo motif analysis, whereas decreased H3K27ac was enriched for v-maf musculoaponeurotic fibrosarcoma oncogene family protein K (MAFK), a known negative regulator of beta cells. By siRNA-mediated knockdown of NRF1, GABPA or MEF2A we found that INS-1 cells exhibited downregulation of fatty acid β-oxidation genes in parallel with decrease in the associated H3K27ac. Furthermore, in line with the epigenome in DIO mice, palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when NRF1, GABPA or MEF2A were suppressed.These results suggest novel roles for DNA-binding proteins and fatty acid signalling in obesity-induced epigenomic regulation of beta cell function.The next-generation sequencing data in the present study were deposited at ArrayExpress. RNA-Seq: Dataset name: ERR2538129 (Control), ERR2538130 (Diet-induced obesity) Repository name and number: E-MTAB-6718 - RNA-Seq of pancreatic islets derived from mice fed a long-term high-fat diet against chow-fed controls. ChIP-Seq: Dataset name: ERR2538131 (Control), ERR2538132 (Diet-induced obesity) Repository name and number: E-MTAB-6719 - H3K27ac ChIP-Seq of pancreatic islets derived from mice fed a long-term high-fat diet (HFD) against chow-fed controls." @default.
• W2895522259 created "2018-10-12" @default.
• W2895522259 creator A5032584020 @default.
• W2895522259 creator A5058349108 @default.
• W2895522259 creator A5076485009 @default.
• W2895522259 creator A5083477042 @default.
• W2895522259 creator A5084726906 @default.
• W2895522259 creator A5085311130 @default.
• W2895522259 creator A5089470172 @default.
• W2895522259 creator A5091149024 @default.
• W2895522259 date "2018-10-03" @default.
• W2895522259 modified "2023-10-16" @default.
• W2895522259 title "Genome-wide profiling of histone H3K27 acetylation featured fatty acid signalling in pancreatic beta cells in diet-induced obesity in mice" @default.
• W2895522259 cites W1960734071 @default.
• W2895522259 cites W1970541810 @default.
• W2895522259 cites W1979594866 @default.
• W2895522259 cites W2001114318 @default.
• W2895522259 cites W2014677321 @default.
• W2895522259 cites W2016317262 @default.
• W2895522259 cites W2021341670 @default.
• W2895522259 cites W2027836023 @default.
• W2895522259 cites W2038961236 @default.
• W2895522259 cites W2046859247 @default.
• W2895522259 cites W2056198580 @default.
• W2895522259 cites W2065103652 @default.
• W2895522259 cites W2073026107 @default.
• W2895522259 cites W2074656730 @default.
• W2895522259 cites W2078059415 @default.
• W2895522259 cites W2082793267 @default.
• W2895522259 cites W2095365870 @default.
• W2895522259 cites W2099057503 @default.
• W2895522259 cites W2114055879 @default.
• W2895522259 cites W2125632841 @default.
• W2895522259 cites W2125805216 @default.
• W2895522259 cites W2126601432 @default.
• W2895522259 cites W2131824619 @default.
• W2895522259 cites W2135190643 @default.
• W2895522259 cites W2140751228 @default.
• W2895522259 cites W2146648681 @default.
• W2895522259 cites W2147332639 @default.
• W2895522259 cites W2151258444 @default.
• W2895522259 cites W2152239989 @default.
• W2895522259 cites W2154141501 @default.
• W2895522259 cites W2154746182 @default.
• W2895522259 cites W2158217645 @default.
• W2895522259 cites W2159482845 @default.
• W2895522259 cites W2177538943 @default.
• W2895522259 cites W2179438025 @default.
• W2895522259 cites W2570136952 @default.
• W2895522259 cites W2576246142 @default.
• W2895522259 cites W2725988230 @default.
• W2895522259 cites W2765177252 @default.
• W2895522259 cites W2782859294 @default.
• W2895522259 cites W2785792383 @default.
• W2895522259 cites W4256409604 @default.
• W2895522259 doi "https://doi.org/10.1007/s00125-018-4735-7" @default.
• W2895522259 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30284014" @default.
• W2895522259 hasPublicationYear "2018" @default.
• W2895522259 type Work @default.
• W2895522259 sameAs 2895522259 @default.
• W2895522259 citedByCount "25" @default.
• W2895522259 countsByYear W28955222592019 @default.
• W2895522259 countsByYear W28955222592020 @default.
• W2895522259 countsByYear W28955222592021 @default.
• W2895522259 countsByYear W28955222592022 @default.
• W2895522259 crossrefType "journal-article" @default.
• W2895522259 hasAuthorship W2895522259A5032584020 @default.
• W2895522259 hasAuthorship W2895522259A5058349108 @default.
• W2895522259 hasAuthorship W2895522259A5076485009 @default.
• W2895522259 hasAuthorship W2895522259A5083477042 @default.
• W2895522259 hasAuthorship W2895522259A5084726906 @default.
• W2895522259 hasAuthorship W2895522259A5085311130 @default.
• W2895522259 hasAuthorship W2895522259A5089470172 @default.
• W2895522259 hasAuthorship W2895522259A5091149024 @default.
• W2895522259 hasBestOaLocation W28955222591 @default.
• W2895522259 hasConcept C101762097 @default.
• W2895522259 hasConcept C104317684 @default.
• W2895522259 hasConcept C111936080 @default.
• W2895522259 hasConcept C121912465 @default.
• W2895522259 hasConcept C134320426 @default.
• W2895522259 hasConcept C150194340 @default.
• W2895522259 hasConcept C153911025 @default.
• W2895522259 hasConcept C190727270 @default.
• W2895522259 hasConcept C2780914512 @default.
• W2895522259 hasConcept C41091548 @default.
• W2895522259 hasConcept C54355233 @default.
• W2895522259 hasConcept C64927066 @default.
• W2895522259 hasConcept C74438686 @default.
• W2895522259 hasConcept C83640560 @default.
• W2895522259 hasConcept C86339819 @default.
• W2895522259 hasConcept C86803240 @default.
• W2895522259 hasConceptScore W2895522259C101762097 @default.
• W2895522259 hasConceptScore W2895522259C104317684 @default.
• W2895522259 hasConceptScore W2895522259C111936080 @default.
• W2895522259 hasConceptScore W2895522259C121912465 @default.
• W2895522259 hasConceptScore W2895522259C134320426 @default.
• W2895522259 hasConceptScore W2895522259C150194340 @default.
• W2895522259 hasConceptScore W2895522259C153911025 @default.

• next