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@ARTICLE{Stefanova:278397,
      author       = {M. E. Stefanova and E. Ing-Simmons and S. Stefanov and I.
                      Flyamer and H. Dorado Garcia and R. Schöpflin and A. G.
                      Henssen$^*$ and J. M. Vaquerizas and S. Mundlos},
      title        = {{D}oxorubicin {C}hanges the {S}patial {O}rganization of the
                      {G}enome around {A}ctive {P}romoters.},
      journal      = {Cells},
      volume       = {12},
      number       = {15},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01631},
      pages        = {2001},
      year         = {2023},
      abstract     = {In this study, we delve into the impact of genotoxic
                      anticancer drug treatment on the chromatin structure of
                      human cells, with a particular focus on the effects of
                      doxorubicin. Using Hi-C, ChIP-seq, and RNA-seq, we explore
                      the changes in chromatin architecture brought about by
                      doxorubicin and ICRF193. Our results indicate that
                      physiologically relevant doses of doxorubicin lead to a
                      local reduction in Hi-C interactions in certain genomic
                      regions that contain active promoters, with changes in
                      chromatin architecture occurring independently of Top2
                      inhibition, cell cycle arrest, and differential gene
                      expression. Inside the regions with decreased interactions,
                      we detected redistribution of RAD21 around the peaks of
                      H3K27 acetylation. Our study also revealed a common
                      structural pattern in the regions with altered architecture,
                      characterized by two large domains separated from each
                      other. Additionally, doxorubicin was found to increase CTCF
                      binding in H3K27 acetylated regions. Furthermore, we
                      discovered that Top2-dependent chemotherapy causes changes
                      in the distance decay of Hi-C contacts, which are driven by
                      direct and indirect inhibitors. Our proposed model suggests
                      that doxorubicin-induced DSBs cause cohesin redistribution,
                      which leads to increased insulation on actively transcribed
                      TAD boundaries. Our findings underscore the significant
                      impact of genotoxic anticancer treatment on the chromatin
                      structure of the human genome.},
      keywords     = {DSBs (Other) / Hi-C (Other) / Top2 (Other) / chemotherapy
                      (Other) / doxorubicin (Other) / promoters (Other)},
      cin          = {BE01},
      ddc          = {570},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37566080},
      pmc          = {pmc:PMC10417312},
      doi          = {10.3390/cells12152001},
      url          = {https://inrepo02.dkfz.de/record/278397},
}