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AURTHO: autoregulation as facilitator of cis-acting element discovery of orthologous transcription factors

Sinaeda Anderssen, Aymeric Naômé, Cédric Jadot, Alain Brans, Pierre Tocquin, Sébastien Rigali
doi: https://doi.org/10.1101/2022.04.06.487287
Sinaeda Anderssen
1InBioS – Center for Protein Engineering, University of Liège, B-4000 Liège, Belgium
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Aymeric Naômé
1InBioS – Center for Protein Engineering, University of Liège, B-4000 Liège, Belgium
2HEDERA 22, Boulevard du Rectorat 27b, B-4000 Liège, Belgium
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Cédric Jadot
1InBioS – Center for Protein Engineering, University of Liège, B-4000 Liège, Belgium
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Alain Brans
1InBioS – Center for Protein Engineering, University of Liège, B-4000 Liège, Belgium
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Pierre Tocquin
2HEDERA 22, Boulevard du Rectorat 27b, B-4000 Liège, Belgium
3InBioS – PhytoSystems, University of Liège, B-4000 Liège, Belgium
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Sébastien Rigali
1InBioS – Center for Protein Engineering, University of Liège, B-4000 Liège, Belgium
2HEDERA 22, Boulevard du Rectorat 27b, B-4000 Liège, Belgium
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  • For correspondence: srigali@uliege.be
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ABSTRACT

Transcriptional regulation is key in bacteria for providing an adequate response in time and space to changing environmental conditions. However, despite decades of research, the binding sites and therefore the target genes and the function of most transcription factors (TFs) remain unknown. Filling this gap in knowledge through conventional methods represents a colossal task which we demonstrate here can be significantly facilitated by a widespread feature in transcriptional control: the autoregulation of TFs implying that the yet unknown transcription factor binding site (TFBS) is neighbouring the TF itself. In this work, we describe the “AURTHO” methodology (AUtoregulation of oRTHOlogous transcription factors), consisting of analyzing upstream regions of orthologous TFs in order to uncover their associated TFBSs. AURTHO enabled the de novo identification of novel TFBSs with an unprecedented improvement in terms of quantity and reliability. DNA-protein interaction studies on a selection of candidate cis-acting elements yielded an >90% success rate, demonstrating the efficacy of AURTHO at highlighting true TF-TFBS couples and confirming the identification in a near future of a plethora of TFBSs across all bacterial species.

Key points

  1. Transcription factor (TF) autoregulation implies that their binding site (TFBS) is in their close vicinity

  2. We developed and assessed the AURTHO methodology (AUtoregulation of oRTHOlogous TFs) for TFBS discovery

  3. Our results shows that AURTHO greatly facilitates the identification of highly reliable novel TFBSs

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/SinaedaA/AURTHO

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 10, 2022.
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AURTHO: autoregulation as facilitator of cis-acting element discovery of orthologous transcription factors
Sinaeda Anderssen, Aymeric Naômé, Cédric Jadot, Alain Brans, Pierre Tocquin, Sébastien Rigali
bioRxiv 2022.04.06.487287; doi: https://doi.org/10.1101/2022.04.06.487287
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AURTHO: autoregulation as facilitator of cis-acting element discovery of orthologous transcription factors
Sinaeda Anderssen, Aymeric Naômé, Cédric Jadot, Alain Brans, Pierre Tocquin, Sébastien Rigali
bioRxiv 2022.04.06.487287; doi: https://doi.org/10.1101/2022.04.06.487287

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