000894918 001__ 894918
000894918 005__ 20220930130326.0
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000894918 020__ $$a978-3-95806-569-7
000894918 037__ $$aFZJ-2021-03480
000894918 041__ $$aEnglish
000894918 1001_ $$0P:(DE-Juel1)171113$$aWiechert, Johanna$$b0$$eCorresponding author$$gfemale$$ufzj
000894918 245__ $$aSilencing and counter-silencing of the Lsr2-like protein CgpS in $\textit{Corynebacterium glutamicumt}$$$f- 2021-11-09
000894918 260__ $$aJülich$$bForschungszentrum Jülich GmbH Zentralbibliothek, Verlag$$c2021
000894918 300__ $$aIV, 265 S.
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000894918 4900_ $$aSchriften des Forschungszentrums Jülich. Reihe Schlüsseltechnologien / Key Technologies$$v243
000894918 502__ $$aUniversität Düsseldorf, Diss., 2020$$bDissertation$$cUniversität Düsseldorf$$d2020
000894918 520__ $$aHorizontal 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. [...]
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000894918 9141_ $$y2021
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