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Open Access Research article

The genome-wide binding profile of the Sulfolobus solfataricus transcription factor Ss-LrpB shows binding events beyond direct transcription regulation

Trong Nguyen-Duc125, Liesbeth van Oeffelen34, Ningning Song3, Gholamreza Hassanzadeh-Ghassabeh12, Serge Muyldermans12, Daniel Charlier3 and Eveline Peeters3*

Author Affiliations

1 Research group of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium

2 Department of Structural Biology, VIB, Pleinlaan 2, B-1050 Brussels, Belgium

3 Research group of Microbiology, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium

4 IMEC, Kapeldreef 75, B-3001 Leuven, Belgium

5 Department of Microbiology and Immunology, State University of New York at Buffalo, 321 Cary Hall, 3435 Main Street, 14214Buffalo, NY, United States

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BMC Genomics 2013, 14:828  doi:10.1186/1471-2164-14-828

Published: 25 November 2013

Abstract

Background

Gene regulatory processes are largely resulting from binding of transcription factors to specific genomic targets. Leucine-responsive Regulatory Protein (Lrp) is a prevalent transcription factor family in prokaryotes, however, little information is available on biological functions of these proteins in archaea. Here, we study genome-wide binding of the Lrp-like transcription factor Ss-LrpB from Sulfolobus solfataricus.

Results

Chromatin immunoprecipitation in combination with DNA microarray analysis (ChIP-chip) has revealed that Ss-LrpB interacts with 36 additional loci besides the four previously identified local targets. Only a subset of the newly identified binding targets, concentrated in a highly variable IS-dense genomic region, is also bound in vitro by pure Ss-LrpB. There is no clear relationship between the in vitro measured DNA-binding specificity of Ss-LrpB and the in vivo association suggesting a limited permissivity of the crenarchaeal chromatin for transcription factor binding. Of 37 identified binding regions, 29 are co-bound by LysM, another Lrp-like transcription factor in S. solfataricus. Comparative gene expression analysis in an Ss-lrpB mutant strain shows no significant Ss-LrpB-mediated regulation for most targeted genes, with exception of the CRISPR B cluster, which is activated by Ss-LrpB through binding to a specific motif in the leader region.

Conclusions

The genome-wide binding profile presented here implies that Ss-LrpB is associated at additional genomic binding sites besides the local gene targets, but acts as a specific transcription regulator in the tested growth conditions. Moreover, we have provided evidence that two Lrp-like transcription factors in S. solfataricus, Ss-LrpB and LysM, interact in vivo.

Keywords:
Archaea; Sulfolobus; Leucine-responsive regulatory protein; CRISPR; ChIP-chip