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@ARTICLE{Wiechert:872604,
      author       = {Wiechert, Johanna and Filipchyk, Andrei and Hünnefeld, Max
                      and Gätgens, Cornelia and Brehm, Jannis and Heermann, Ralf
                      and Frunzke, Julia},
      title        = {{D}eciphering the {R}ules {U}nderlying {X}enogeneic
                      {S}ilencing and {C}ounter-{S}ilencing of {L}sr2-like
                      {P}roteins {U}sing {C}gp{S} of {C}orynebacterium glutamicum
                      as a {M}odel},
      journal      = {mBio},
      volume       = {11},
      number       = {1},
      issn         = {2150-7511},
      address      = {Washington, DC},
      publisher    = {American Society for Microbiology},
      reportid     = {FZJ-2020-00097},
      pages        = {e02273-19/mbio/11/1/mBio.02273-19.atom},
      year         = {2020},
      abstract     = {Lsr2-like nucleoid-associated proteins play an important
                      role as xenogeneic silencers (XS) of horizontally acquired
                      genomic regions in actinobacteria. In this study, we
                      systematically analyzed the in vivo constraints underlying
                      silencing and counter-silencing of the Lsr2-like protein
                      CgpS in Corynebacterium glutamicum. Genome-wide analysis
                      revealed binding of CgpS to regions featuring a distinct
                      drop in GC profile close to the transcription start site
                      (TSS) but also identified an overrepresented motif with
                      multiple A/T steps at the nucleation site of the
                      nucleoprotein complex. Binding of specific transcription
                      factors (TFs) may oppose XS activity, leading to
                      counter-silencing. Following a synthetic counter-silencing
                      approach, target gene activation was realized by inserting
                      operator sites of an effector-responsive TF within various
                      CgpS target promoters, resulting in increased promoter
                      activity upon TF binding. Analysis of reporter constructs
                      revealed maximal counter-silencing when the TF operator site
                      was inserted at the position of maximal CgpS coverage. This
                      principle was implemented in a synthetic toggle switch,
                      which features a robust and reversible response to effector
                      availability, highlighting the potential for
                      biotechnological applications. Together, our results provide
                      comprehensive insights into how Lsr2 silencing and
                      counter-silencing shape evolutionary network expansion in
                      this medically and biotechnologically relevant bacterial
                      phylum.},
      cin          = {IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {581 - Biotechnology (POF3-581) / DFG project 218313974 -
                      Spontane Induktion kryptischer Prophagen in Populationen der
                      Modellorganismen Corynebacterium glutamicum und Escherichia
                      coli},
      pid          = {G:(DE-HGF)POF3-581 / G:(GEPRIS)218313974},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32019787},
      UT           = {WOS:000518763400112},
      doi          = {10.1128/mBio.02273-19},
      url          = {https://juser.fz-juelich.de/record/872604},
}