title: High-Resolution 4C Reveals Rapid p53-Dependent Chromatin Reorganization of the CDKN1A Locus in Response to Stress.
abstract: A regulatory program involving hundreds of genes is coordinated by p53 to prevent carcinogenesis in response to stress. Given the importance of chromatin loops in gene regulation, we investigated whether DNA interactions participate in the p53 stress response. To shed light on this issue, we measured the binding dynamics of cohesin in response to stress. We reveal that cohesin is remodeled at specific loci during the stress response and that its binding within genes negatively correlates with transcription. At p53 target genes, stress-induced eviction of cohesin from gene bodies is concomitant to spatial reorganization of loci through the disruption of functional chromatin loops. These findings demonstrate that chromatin loops can be remodeled upon stress and contribute to the p53-driven stress response. Additionally, we also propose a mechanism whereby transcription-coupled eviction of cohesin from CDKN1A might act as a molecular switch to control spatial interactions between regulatory elements.
authors.affiliation: Départment de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Millau
authors.affiliation: Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wijchers
authors.affiliation: Départment de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
authors.forename: Luc
authors.initials: L
authors.lastname: Gaudreau
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D003630:Daunorubicin / Q000633:toxicity; D017930:Genes, Reporter; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D003630:Daunorubicin; D055436:Growth Differentiation Factor 15; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C526140:GDF15 protein, human; C429022:RAD21 protein, human