| 1. |
- Aurell, Erik, et al.
(författare)
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Transcription factor concentrations versus binding site affinities in the yeast S. cerevisiae
- 2007
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Ingår i: Physical Biology. - : IOP Publishing. - 1478-3975. ; 4:2, s. 134-143
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Tidskriftsartikel (refereegranskat)abstract
- Transcription regulation is largely governed by the profile and the dynamics of transcription factors' binding to DNA. Stochastic effects are intrinsic to this dynamics, and the binding to functional sites must be controlled with a certain specificity for living organisms to be able to elicit specific cellular responses. Specificity stems here from the interplay between binding affinity and cellular abundance of transcription factor proteins, and the binding of such proteins to DNA is thus controlled by their chemical potential. We combine large-scale protein abundance data in the budding yeast with binding affinities for all transcription factors with known DNA binding site sequences to assess the behavior of their chemical potentials in an exponential growth phase. A sizable fraction of transcription factors is apparently bound non-specifically to DNA, and the observed abundances are marginally sufficient to ensure high occupations of the functional sites. We argue that a biological cause of this feature is related to its noise-filtering consequences: abundances below physiological levels do not yield significant binding of functional targets and mis-expressions of regulated genes may thus be tamed.
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| 2. |
- Fouquier d'Hérouel, Aymeric, et al.
(författare)
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A simple and efficient method to search for selected primary transcripts : non-coding and antisense RNAs in the human pathogen Enterococcus faecalis
- 2011
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:7, s. E46-
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Tidskriftsartikel (refereegranskat)abstract
- Enterococcus faecalis is a commensal bacterium and a major opportunistic human pathogen. In this study, we combined in silico predictions with a novel 5'RACE-derivative method coined '5'tagRACE', to perform the first search for non-coding RNAs (ncRNAs) encoded on the E. faecalis chromosome. We used the 5'tagRACE to simultaneously probe and characterize primary transcripts, and demonstrate here the simplicity, the reliability and the sensitivity of the method. The 5'tagRACE is complementary to tiling arrays or RNA-sequencing methods, and is also directly applicable to deep RNA sequencing and should significantly improve functional studies of bacterial RNA landscapes. From 45 selected loci of the E. faecalis chromosome, we discovered and mapped 29 novel ncRNAs, 10 putative novel mRNAs and 16 antisense transcriptional organizations. We describe in more detail the oxygen-dependent expression of one ncRNA located in an E. faecalis pathogenicity island, the existence of an ncRNA that is antisense to the ncRNA modulator of the RNA polymerase, SsrS and provide evidences for the functional interplay between two distinct toxin-antitoxin modules.
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| 3. |
- Fouquier d’Hérouël, Aymeric, et al.
(författare)
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FR-like EBNA1 binding repeats in the human genome
- 2010
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Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 405:2, s. 524-529
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Tidskriftsartikel (refereegranskat)abstract
- Epstein Barr Virus (EBV) is widely spread in the human population. EBV nuclear antigen 1 (EBNA1) is a transcription factor that activates viral genes and is necessary for viral replication and partitioning, which binds the EBV genome cooperatively. We identify similar EBNA1 repeat binding sites in the human genome using a nearest-neighbour positional weight matrix. Previously experimentally verified EBNA1 sites in the human genome are successfully recovered by our approach. Most importantly, 40 novel regions are identified in the human genome, constituted of tandemly repeated binding sites for EBNA1. Genes located in vicinity of these regions are presented as possible targets for EBNA1-mediated regulation. Among these, four are discussed in more detail: IQCB1, IMPG1, IRF2BP and TPO. Incorporating the cooperative actions of EBNA1 is essential when identifying regulatory regions in the human genome and we believe the findings presented here are highly valuable for the understanding of EBV-induced phenotypic changes.
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| 4. |
- Fouquier d'Hérouël, Aymeric
(författare)
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QPS - quadratic programming sampler : a motif finder using biophysical modeling
- 2008
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We present a Markov chain Monte Carlo algorithm for local alignments of nucleotide sequences aiming to infer putative transcription factor binding sites, referred to as the quadratic programming sampler. The new motif nder incorporates detailed biophysical modeling of the transcription factor binding site recognition which arises an intrinsic threshold discriminating putative binding sites from other/background sequences. We validate the principal functioning of the algorithm on a sample of four promoter regions from Escherichia coli. The resulting description of the motif can be readily evaluated on the whole genome to identify new putative binding sites.
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| 5. |
- Fouquier d'Herouel, Aymeric, 1980-
(författare)
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Statistical models of TF/DNA interaction
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gene expression is regulated in response to metabolic necessities and environmental changes throughout the life of a cell. A major part of this regulation is governed at the level of transcription, deciding whether messengers to specific genes are produced or not. This decision is triggered by the action of transcription factors, proteins which interact with specific sites on DNA and thus influence the rate of transcription of proximal genes. Mapping the organisation of these transcription factor binding sites sheds light on potential causal relations between genes and is the key to establishing networks of genetic interactions, which determine how the cell adapts to external changes. In this work I review briefly the basics of genetics and summarise popular approaches to describe transcription factor binding sites, from the most straight forward to finally discuss a biophysically motivated representation based on the estimation of free energies of molecular interactions. Two articles on transcription factors are contained in this thesis, one published (Aurell, Fouquier d'Hérouël, Malmnäs and Vergassola, 2007) and one submitted (Fouquier d'Hérouël, 2008). Both rely strongly on the representation of binding sites by matrices accounting for the affinity of the proteins to specific nucleotides at the different positions of the binding sites. The importance of non-specific binding of transcription factors to DNA is briefly addressed in the text and extensively discussed in the first appended article: In a study on the affinity of yeast transcription factors for their binding sites, we conclude that measured in vivo protein concentrations are marginally sufficient to guarantee the occupation of functional sites, as opposed to unspecific emplacements on the genomic sequence. A common task being the inference of binding site motifs, the most common statistical method is reviewed in detail, upon which I constructed an alternative biophysically motivated approach, exemplified in the second appended article.
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| 6. |
- Innocenti, Nicolas, 1986-, et al.
(författare)
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An observation of circular RNAs in bacterial RNA-seq data.
- 2015
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Circular RNAs (circRNAs) are a class of RNA with an important role in micro RNA (miRNA) regulation recently discovered in Human and various other eukaryotes as well as in archaea. Here, we have analyzed RNA-seq data obtained from Enterococcus faecalis and Escherichia coli in a way similar to previous studies performed on eukaryotes. We report observations of circRNAs in RNA-seq data that are reproducible across multiple experiments performed with different protocols or growth conditions.
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| 7. |
- Innocenti, Nicolas, 1986-, et al.
(författare)
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Whole-genome mapping of 5′ RNA ends in bacteria by tagged sequencing: a comprehensive view in Enterococcus faecalis
- 2015
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Ingår i: RNA. - : RNA Society. - 1355-8382 .- 1469-9001.
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Tidskriftsartikel (refereegranskat)abstract
- Enterococcus faecalis is the third cause of nosocomial infections. To obtain the first snapshot of transcriptional organizations in this bacterium, we used a modified RNA-seq approach enabling to discriminate primary from processed 5' RNA ends. We also validated our approach by confirming known features in Escherichia coli. We mapped 559 transcription start sites (TSSs) and 352 processing sites (PSSs) in E. faecalis. A blind motif search retrieved canonical features of SigA-and SigN-dependent promoters preceding transcription start sites mapped. We discovered 85 novel putative regulatory RNAs, small-and antisense RNAs, and 72 transcriptional antisense organizations. Presented data constitute a significant insight into bacterial RNA landscapes and a step toward the inference of regulatory processes at transcriptional and post-transcriptional levels in a comprehensive manner.
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| 8. |
- Lacoux, Caroline, et al.
(författare)
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Dynamic insights on transcription initiation and RNA processing during bacterial adaptation
- 2020
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Ingår i: RNA. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 1355-8382 .- 1469-9001. ; 26:4, s. 382-395
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Tidskriftsartikel (refereegranskat)abstract
- Transcription initiation and RNA processing govern gene expression and enable bacterial adaptation by reshaping the RNA landscape. The aim of this study was to simultaneously observe these two fundamental processes in a transcriptome responding to an environmental signal. A controlled sigma(E) system in E. coli was coupled to our previously described tag RNAseq method to yield process kinetics information. Changes in transcription initiation frequencies (TIF) and RNA processing frequencies (PF) were followed using 5' RNA tags. Changes in TIF showed a binary increased/decreased pattern that alternated between transcriptionally activated and repressed promoters, providing the bacterial population with transcriptional oscillation. PF variation fell into three categories of cleavage activity: (i) constant and independent of RNA levels, (ii) increased once RNA has accumulated, and (iii) positively correlated to changes in TIF. This work provides a comprehensive and dynamic view of major events leading to transcriptomic reshaping during bacterial adaptation. It unveils an interplay between transcription initiation and the activity of specific RNA cleavage sites. This study utilized a well-known genetic system to analyze fundamental processes and can serve as a blueprint for comprehensive studies that exploit the RNA metabolism to decipher and understand bacterial gene expression control.
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