Papantonis, Argyris

[["dc.bibliographiccitation.artnumber","3014"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kargapolova, Yulia"],["dc.contributor.author","Rehimi, Rizwan"],["dc.contributor.author","Kayserili, Hülya"],["dc.contributor.author","Brühl, Joanna"],["dc.contributor.author","Sofiadis, Konstantinos"],["dc.contributor.author","Zirkel, Anne"],["dc.contributor.author","Palikyras, Spiros"],["dc.contributor.author","Mizi, Athanasia"],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Papantonis, Argyris"],["dc.date.accessioned","2021-06-01T10:50:39Z"],["dc.date.available","2021-06-01T10:50:39Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance."],["dc.description.sponsorship","Open-Access-Finanzierung durch die Universitätsmedizin Göttingen 2021"],["dc.identifier.doi","10.1038/s41467-021-23327-1"],["dc.identifier.pmid","34021162"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86739"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/278"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2041-1723"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","CC BY 4.0"],["dc.title","Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Molecular Systems Biology"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Sofiadis, Konstantinos"],["dc.contributor.author","Josipovic, Natasa"],["dc.contributor.author","Nikolic, Milos"],["dc.contributor.author","Kargapolova, Yulia"],["dc.contributor.author","Übelmesser, Nadine"],["dc.contributor.author","Varamogianni‐Mamatsi, Vassiliki"],["dc.contributor.author","Zirkel, Anne"],["dc.contributor.author","Papadionysiou, Ioanna"],["dc.contributor.author","Loughran, Gary"],["dc.contributor.author","Papantonis, Argyris"],["dc.contributor.author","Keane, James"],["dc.contributor.author","Michel, Audrey"],["dc.contributor.author","Gusmao, Eduardo G"],["dc.contributor.author","Becker, Christian"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Georgomanolis, Theodore"],["dc.contributor.author","Mizi, Athanasia"],["dc.date.accessioned","2021-08-12T07:45:39Z"],["dc.date.available","2021-08-12T07:45:39Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Spatial organization and gene expression of mammalian chromosomes are maintained and regulated in conjunction with cell cycle progression. This is perturbed once cells enter senescence and the highly abundant HMGB1 protein is depleted from nuclei to act as an extracellular proinflammatory stimulus. Despite its physiological importance, we know little about the positioning of HMGB1 on chromatin and its nuclear roles. To address this, we mapped HMGB1 binding genome‐wide in two primary cell lines. We integrated ChIP‐seq and Hi‐C with graph theory to uncover clustering of HMGB1‐marked topological domains that harbor genes involved in paracrine senescence. Using simplified Cross‐Linking and Immuno‐Precipitation and functional tests, we show that HMGB1 is also a bona fide RNA‐binding protein (RBP) binding hundreds of mRNAs. It presents an interactome rich in RBPs implicated in senescence regulation. The mRNAs of many of these RBPs are directly bound by HMGB1 and regulate availability of SASP‐relevant transcripts. Our findings reveal a broader than hitherto assumed role for HMGB1 in coordinating chromatin folding and RNA homeostasis as part of a regulatory loop controlling cell‐autonomous and paracrine senescence."],["dc.description.abstract","Synopsis image Mammalian cell senescence entry is marked by the nuclear loss of HMGB1. Genome‐wide analyses show that HMGB1 binds both chromatin and mRNAs in proliferating cells, and its loss underlies topological and splicing changes inducing the senescent transcriptional program. Senescence entry by mammalian cells is marked by the nuclear depletion of HMGB1. HMGB1 shows dual specificity binding to a subset of topological boundaries on chromatin and to hundreds of mRNAs. TAD clusters enriched for HMGB1 spatially co‐associate in proliferating cell nuclei. HMGB1 loss leads to transcriptional changes necessary for senescence establishment."],["dc.description.abstract","Mammalian cell senescence entry is marked by the nuclear loss of HMGB1. Genome‐wide analyses show that HMGB1 binds both chromatin and mRNAs in proliferating cells, and its loss underlies topological and splicing changes inducing the senescent transcriptional program. image"],["dc.description.sponsorship","German Research Foundation (DFG) http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Else‐Kroener‐Fresenius‐Stiftung"],["dc.description.sponsorship","International Max Planck Research School for Genome Science"],["dc.description.sponsorship","Irish Research Council http://dx.doi.org/10.13039/501100002081"],["dc.description.sponsorship","Erasmus+ Mobility funds"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.15252/msb.20209760"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88520"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.issn","1744-4292"],["dc.relation.orgunit","Institut für Pathologie"],["dc.rights","CC BY 4.0"],["dc.title","HMGB1 coordinates SASP‐related chromatin folding and RNA homeostasis on the path to senescence"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e101533"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Weiterer, Sinah‐Sophia"],["dc.contributor.author","Meier‐Soelch, Johanna"],["dc.contributor.author","Georgomanolis, Theodore"],["dc.contributor.author","Mizi, Athanasia"],["dc.contributor.author","Beyerlein, Anna"],["dc.contributor.author","Weiser, Hendrik"],["dc.contributor.author","Brant, Lilija"],["dc.contributor.author","Mayr‐Buro, Christin"],["dc.contributor.author","Jurida, Liane"],["dc.contributor.author","Beuerlein, Knut"],["dc.contributor.author","Müller, Helmut"],["dc.contributor.author","Weber, Axel"],["dc.contributor.author","Tenekeci, Ulas"],["dc.contributor.author","Dittrich‐Breiholz, Oliver"],["dc.contributor.author","Bartkuhn, Marek"],["dc.contributor.author","Nist, Andrea"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","IJcken, Wilfred FJ"],["dc.contributor.author","Riedlinger, Tabea"],["dc.contributor.author","Schmitz, M Lienhard"],["dc.contributor.author","Papantonis, Argyris"],["dc.contributor.author","Kracht, Michael"],["dc.date.accessioned","2019-12-05T15:22:53Z"],["dc.date.accessioned","2021-10-27T13:21:48Z"],["dc.date.available","2019-12-05T15:22:53Z"],["dc.date.available","2021-10-27T13:21:48Z"],["dc.date.issued","2019"],["dc.description.abstract","How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1α induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF-κB at regions that are highly enriched for inflammatory disease-relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL-1α-inducible IL8 and CXCL1-3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL-1α/TAK1-inducible manner. Microdeletions of p65-binding sites in either of the two enhancers impair NF-κB recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher-order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 \"master\" enhancer in the regulation of sustained IL-1α signaling, as well as for IL-8 and IL-6 secretion. CRISPR-guided transactivation of the IL8 locus or cross-TAD regulation by TNFα-responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF-κB."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaſt (DFG) http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","Deutsche Krebshilfe http://dx.doi.org/10.13039/501100005972"],["dc.description.sponsorship","Max‐Planck Society http://dx.doi.org/10.13039/501100004189"],["dc.description.sponsorship","Excellence Cluster Cardio‐Pulmonary System and Cardio‐Pulmonary Institute (EXC 147: Kardiopulmonales System)"],["dc.description.sponsorship","Cardio‐Pulmonary Institute (CPI)"],["dc.description.sponsorship","DZL/UGMLC Program"],["dc.description.sponsorship","Center for Molecular Medicine Cologne (ZMMK)"],["dc.identifier.doi","10.15252/embj.2019101533"],["dc.identifier.isbn","31701553"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16860"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92046"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1460-2075"],["dc.relation.issn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Distinct IL‐1α‐responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]