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@PHDTHESIS{Wiechert:894918,
      author       = {Wiechert, Johanna},
      title        = {{S}ilencing and counter-silencing of the {L}sr2-like
                      protein {C}gp{S} in $\textit{{C}orynebacterium
                      glutamicumt}$},
      volume       = {243},
      school       = {Universität Düsseldorf},
      type         = {Dissertation},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {FZJ-2021-03480},
      isbn         = {978-3-95806-569-7},
      series       = {Schriften des Forschungszentrums Jülich. Reihe
                      Schlüsseltechnologien / Key Technologies},
      pages        = {IV, 265 S.},
      year         = {2021},
      note         = {Universität Düsseldorf, Diss., 2020},
      abstract     = {Horizontal gene transfer (HGT) is a major driving force of
                      microbial evolution as it allows the rapid acquisition of
                      new genetic traits. However, foreign DNA is likely to
                      decrease the fitness of recipient cells by causing
                      detrimental effects and therefore requires stringent control
                      of gene expression. Hence, bacteria evolved a number of
                      mechanisms allowing them to discriminate between self and
                      non-self. Xenogeneic silencer (XS) proteins are
                      nucleoid-associated proteins that preferentially bind to
                      horizontally acquired DNA based on differences in nucleotide
                      composition, in particular a higher AT content. XS proteins
                      are widely distributed in bacteria and belong to one of the
                      four classes comprising the H-NS-like XS, Rok, MvaT/U-like
                      proteins, and Lsr2-like XS proteins. They play a predominant
                      role in the acquisition of novel genetic material and
                      oligomerization of XS proteins to higher-order nucleoprotein
                      complexes tightly inhibits transcription. Binding of a
                      transcription factor (TF) within a silenced region may
                      interfere with the XS-DNA complex leading to
                      counter-silencing and activation of gene expression.
                      Consequently, XS and counter-silencing facilitate the
                      integration of novel genetic material into host regulatory
                      circuits enabling the appropriate expression in response to
                      physiological and environmental stimuli. The aim of this
                      thesis was to investigate the rules underlying silencing and
                      counter-silencing of the medically and biotechnologically
                      relevant Lsr2-like proteins conserved in actinobacteria by
                      using CgpS from $\textit{Corynebacterium glutamicum}$ as a
                      model. CgpS has previously been identified as an Lsr2-like
                      XS, which is crucial for maintaining the lysogenic state of
                      an AT-rich, cryptic prophage element. In this thesis,
                      genome-wide bioinformatic analyses showed that CgpS
                      preferentially binds to long and consecutive AT-rich
                      stretches and that CgpS targets typically feature a distinct
                      drop in GC-profile close tothe transcriptional start site
                      (TSS). Furthermore, a sequence-specific binding motif
                      containing multiple A/T steps was overrepresented in CgpS
                      bound regions. The importance of the drop in GC-profile and
                      the putative binding motif for CgpS silencing was verified
                      by performing in vivo reporter studies with synthetic
                      variants of native CgpS target promoters, demonstrating that
                      both DNA features cooperatively support CgpS-mediated
                      silencing. [...]},
      cin          = {IBG-1},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:0001-2021110919},
      url          = {https://juser.fz-juelich.de/record/894918},
}