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| Home > Publications database > Silencing and counter-silencing of the Lsr2-like protein CgpS in $\textit{Corynebacterium glutamicumt}$ |
| Home > Publications database > Silencing and counter-silencing of the Lsr2-like protein CgpS in $\textit{Corynebacterium glutamicumt}$ |
| Book/Dissertation / PhD Thesis | FZJ-2021-03480 |
2021
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
ISBN: 978-3-95806-569-7
Please use a persistent id in citations: http://hdl.handle.net/2128/28951 urn:nbn:de:0001-2021110919
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. [...]
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